International Immunology, Vol. 12, No. 11, 1539-1546,
November 2000
© 2000 Japanese Society for Immunology
Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-
B pathway
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, MC1601, Farmington, CT 06030-1601, USA
Correspondence to: P. K. Srivastava
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Abstract |
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Dendritic cells (DC) are key components of innate and adaptive immune responses. The identity of endogenous signals that activate DC is a crucial and unresolved question. We report here that heat shock proteins (HSP), the most abundant and conserved mammalian molecules, constitute such an internal signal. Necrotic but not apoptotic cell death leads to release of HSP gp96, calreticulin, hsp90 and hsp70. HSP stimulate macrophages to secrete cytokines, and induce expression of antigen-presenting and co-stimulatory molecules on the DC. The HSP gp96 and hsp70 act differentially, and each induces some but not all molecules. HSP interact with these antigen-presenting cells through the highly conserved NF-
B pathway. As HSP are intracellular, abundant and soluble, their presence in the extra-cellular milieu and the consequent activation of antigen-presenting cells (APC) constitutes an excellent mechanism for response to cell death. As HSP are conserved from bacteria to mammals, the ability of HSP to activate APC provides a unified mechanism for response to internal and external stimuli.
Keywords: cytokines, hsp70, hsp90, innate immunity, gp96
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Introduction |
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Our previous studies have shown that microgram quantities of heat shock protein (HSP)–peptide complexes can immunize rats, mice, frogs (see 1) and humans (2), and elicit specific T cell responses. The mechanism through which HSP–peptide complexes elicit T cell responses has been elucidated partially (3). HSP interact with HSP receptors on antigen-presenting cells (APC) such as macrophages and dendritic cells (DC) (4,5); the HSP–peptide complexes are taken up into non-acidic compartments, and the peptides are processed and re-presented by the MHC I molecules of the APC. The HSP–APC interaction lies therefore at the heart of the unusually potent immunogenicity of the HSP–peptide complexes.
During our analysis of the HSP–APC interaction, we have become aware of a novel aspect of HSP function. We observe that HSP stimulate macrophages to elaborate cytokines and induce expression of higher levels of co-stimulatory molecules on the DC. These phenomena occur with the involvement of the NF-B pathway. The new properties of HSP, as reported here, are reminiscent of those of bacterial products such as lipopolysaccharides (LPS) or of certain cytokines, which are secondary activators of DC. HSP are shown here to be the first products of autologous (mammalian) origin which are primary activators of DC. Our observations suggest a key role for HSP–APC interaction in the maintenance and potentiation of innate immunity, in addition to the previously documented role of such interaction in eliciting adaptive responses to the HSP-chaperoned peptides.
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Methods |
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HSP, antibodies and LPS antagonist
hsp90, hsp70 and gp96 were purified simultaneously from C57BL/6 mouse liver as described (6). Antibodies against CD80 or B7-1 (clone 16-10A1), CD86 or B7-2 (GL1), CD40 (3/23), CD11b (M1/70), CD11c (HL3) and MHC II (clone AF6-120.1) for FACS analysis were purchased from PharMingen (San Diego, CA). LPS antagonist Rslp was obtained from Dr Niloufer Qureshi.
Assay of LPS content
The LPS content was measured by the limulus amebocyte lysate (LAL) assay (LAL kit QCL-1000; Biowhittaker, Walkersville, MD).
Preparation of necrotic and apoptotic cells
Cells were frozen and thawed through four cycles of liquid nitrogen–room temperature treatments in order to mimic necrosis. Cells were irradiated (7500 rad) in order to initiate apoptosis.
Generation of bone marrow-derived DC
Femurs and tibia of C57BL/6 mice were removed. The marrow was flushed out from the bones with media and leukocytes obtained were cultured as described (7).
Cytokine assay
Cells (5x104 or 3x104 as indicated) were incubated for 20 h at 37°C in complete medium with 5% FCS, or with increasing quantities of HSP, in 96-well, flat-bottom plates. Supernatants were harvested and assayed by ELISA for tumor necrosis factor (TNF)-
, IL-12, IL-1ß, granulocyte macrophage colony stimulating factor (GM-CSF) and IFN-
. IL-1ß, TNF-, GM-CSF and IFN- kits were purchased from Endogen (Woburn, MA), and the IL-12 kit was purchased from R&D Systems (Minneapolis, MN).
Preparation of nuclear extracts and electrophoretic mobility shift assay
APC were washed with PBS (LPS-free) and re-suspended in cold lysis buffer [buffer A: 10 mM HEPES (pH 7.9), 10 mM KCl, 0.1 mM EDTA, 0.1 mM EGTA, 1 mM DTT, 0.5 mM PMSF, 1 µM aprotinin, 1 µM pepstatin and 14 µM leupeptin] with 0.1% NP-40 and incubated on ice for 30 min. Nuclei were pelleted at 14,000 r.p.m. for 2 min at 4°C. Proteins were extracted from the nuclei in a hypertonic buffer [buffer C: 20 mM HEPES (pH 7.9), 0.4M NaCl, 1 mM EDTA, 1 mM EGTA, 1 mM DTT, 1 mM PMSF, 1 µM aprotinin, 1 µM pepstatin and 14 µM leupeptin] on ice for 30 min (mixing frequently by vortexing). Nuclear debri was pelleted at 14,000 r.p.m. for 5 min at 4°C. Supernatant was collected and protein concentration was measured by Bradford assay. The standard DNA-binding reaction was performed using B DNA probe (5'-AGTTGAGGGGACTTTCCCAGGC-3'), as described (8).
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Results |
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Necrotic but not apoptotic cells release HSP
Cell death can be achieved in a variety of ways, popularly classified into two: apoptotic and necrotic. We have asked which of these two forms of death can result in release of the major HSP: hsp70, hsp90, calreticulin (CRT) and gp96. E.G7 cells were subjected to a freeze–thaw procedure as a necrosis-mimetic or were irradiated as a form of apoptosis-mimetic process, as described in Methods. Cells were checked for necrosis visually under the microscope, and for apoptosis by externalization of phosphatidyl serine (as detected by staining with Annexin V) and degradation of PARP by caspases (data not shown) (9). The supernatants of the treated cells were collected immediately after treatment or 24 h after treatment by either method, and analyzed by SDS–PAGE and immunoblotting with antibodies to the four HSP. It was observed that necrotic but not apoptotic death led to release of all four HSP (Fig. 1
). No HSP were detected in the supernatants of apoptotic cells even 24 h after death.
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HSP stimulate macrophages to secrete cytokines
Three major HSP, hsp90 and gp96 (of the hsp90 family) and hsp70, were tested. hsp90 and hsp70 are cytosolic proteins, whereas gp96 is localized to the endoplasmic reticulum. Approximately 30–100 µg gp96, 200 µg hsp70 and 400 µg hsp90 can be isolated in purified form from 2–5x108 cells. Altogether, these three HSP constitute the most abundant soluble components (>2% of the total protein) of the mammalian cells. Homogenous preparations of the three HSP were obtained from livers of C57BL/6 mice as described in Methods (Fig. 2A
) and were identified by immunoblotting with respective mAb (data not shown). Peritoneal cells from mice previously injected i.p. with pristane were positively selected for CD11b+ cells as described in Methods and then cultured in vitro with increasing quantities of gp96 for 20 h at 37°C. Supernatants were harvested and tested for the presence of IL-1ß, TNF-, GM-CSF and IL-12, and as a negative control, IFN-, by ELISA (Fig. 2B). Treatment with anti-CD11b antibody during or after positive selection did not result in activation of the cells. gp96 was found to stimulate in a titratable manner secretion of all the cytokines tested, except IFN- (data not shown). Similar results were obtained with hsp90 and hsp70, but not with control proteins histone, ovalbumin and insulin (Fig. 2B). Although gp96 was the most potent inducer of the four cytokines at comparable protein quantities, it is the least abundant among the HSP tested. hsp90 therefore appears to be the most significant stimulator on a per cell equivalent basis when one considers that it is the most abundant among the HSP.
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The ability of HSP to stimulate APC does not derive from contaminating LPS
Because LPS is a known and potent stimulator of APC, HSP were purified by the deliberate use of Good Manufacturing Practices of the Food and Drug Administration and the resulting HSP preparations were shown to be free of detectable levels of LPS (<0.02 EU in absolute quantity) by the LAL assay. The possibility of contribution of LPS was tested by two independent parameters. Activation of APC by LPS, particularly at low concentrations of LPS, is dependent upon the presence of the LPS-binding protein (LBP) normally present in serum (10,11). gp96 preparations were tested for their ability to stimulate secretion of IL-1ß by macrophages in medium with and without serum. The activity of gp96 was found to be entirely serum-independent. In contrast, the activity of LPS in a similar assay was highly sensitive to the presence of serum (Fig. 3A
). As yet another test for potential contamination of HSP by LPS, an antagonist (competitive inhibitor) of LPS, derived from Rhodopseudomonas spheroides, was used (14). This inhibitor (Rslp) diminished the ability of LPS but not gp96 to stimulate secretion of IL-1ß by >75%. In fact, the activity of gp96 was greater in presence of Rslp (Fig. 3B). Other points of distinction were observed between LPS and HSP and these are indicated elsewhere (see Fig. 5 and attendant text). Other control experiments were performed to rule out the possibility of contaminating LPS being responsible for the activity observed by us. These included boiling and trypsin treatment of the HSP preparations and LPS. In each case tested, the APC-stimulatory activity of HSP preparations was sensitive to both treatments, while the corresponding activity of LPS preparations was resistant to both (data not shown).
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HSP stimulate DC to express antigen-presenting and co-stimulatory molecules
The effect of HSP on maturation of DC was examined. Homogenous, LPS-free preparations of the HSP gp96 and hsp70 were obtained from livers of C57BL/6 mice. Bone marrow-derived DC, obtained by culturing in GM-CSFcontaining medium (7), were pulsed with gp96 or hsp70, or with LPS (as a positive control) or serum albumin (as a negative control). The pulsed DC were tested for surface expression of MHC II, B7-1, B7-2 and CD40 molecules. LPS induced expression of all markers tested, except B7-1. We attribute this result to a relatively high proportion of B7-1+ cells in the starting DC culture. gp96 (400 µg/ml) was observed to induce a high degree of expression of MHC II and the co-stimulatory molecule B7-2, but not B7-1 nor CD40 (Fig. 4
). hsp70 (400 µg/ml), on the other hand, elicited a modest stimulation of surface expression of B7-2 but not B7-1, nor MHC II and CD40. The complete lack of stimulation of CD40 expression by gp96 or hsp70 led us to test this phenomenon more extensively and at a range of concentrations of the HSP (40–400 µg/ml); however, CD40 expression was not induced at any concentration tested. Serum albumin (400 µg/ml), in the same buffer as the HSP, did not induce expression of any of the markers tested.
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Activation of APC by HSP activates translocation of NF-
BThe mechanism through which gp96 interacts with APC was investigated, with reference to the activation of the NF-
B pathway, shown previously (12) to be a key transcriptional regulator for several cytokines and other immunologically important molecules. This pathway has also been shown to be activated in response to LPS and to be involved in the maturation of DC (13). Primary cultures of CD11c+ cells were pulsed with gp96 or LPS and cells were harvested at various time intervals. Nuclear extracts from the samples were used for binding to NF-B-specific oligomers and were resolved by native PAGE. It was observed that gp96 activates the transduction pathway and does so with a kinetics distinctly different from that of LPS (Fig. 5
). The nuclear translocation of NF-B is seen in gp96-treated DC as early as 15 min after pulsing and the signal diminishes to background levels by 120 min. In contrast, the translocation in LPS-treated DC has a slower initiation kinetics. The differences in the kinetics of translocation of NF-B between gp96 and LPS as seen here is not a function of the quantities of either agent. Exposure of DC to graded quantities of each shows the same differences in kinetics (data not shown). In addition to providing a key glimpse into the mechanism through which HSP activate APC, these studies show the extent to which the effects of LPS and HSP on APC are similar yet distinct.
Necrotic but not apoptotic lysates deliver a maturation signal and cause translocation of NF-B
In view of the data shown in Fig. 5, and in view of the recent demonstration by Gallucci et al. (14) and Sauter et al. (15) that necrotic but not apoptotic cells mediate maturation of DC, we tested whether exposure of DC to necrotic or apoptotic cells leads to translocation of NF-B to the nucleus. Cultures of immature DC were exposed to necrotic or apoptotic E.G7 cells (prepared as described in Methods), and were monitored for expression of MHC II, B7-1, B7-2 and CD40. Exposure of DC to necrotic but not apoptotic cells elicited expression of each of the maturation markers on the DC (Fig. 6A). Interestingly, although purified gp96 or hsp70 did not stimulate expression of CD40 (Fig. 4), the necrotic lysate did (Fig. 6A). The possible significance of this observation is commented upon in Discussion. The DC cultures exposed to medium, or necrotic or apoptotic lysates were also tested for translocation of NF-B. Consistent with the observations in Fig. 5, necrotic but not apoptotic supernatants mediated translocation of NF-B to the nucleus (Fig. 6B). While these observations do not prove that the HSP in the necrotic lysates are the causative agents of this translocation, they are definitely consistent with that observation.
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Discussion |
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HSP are intracellular molecules and the physiological relevance of their ability to activate APC may not be immediately obvious. However, being the most abundant, soluble, intracellular molecules, the presence of HSP in the extracellular milieu would act an excellent message alerting the APC to physical damage of the surrounding cells, whether as a consequence of bacterial and viral infections or mechanical injury. The ability of this signal to activate APC can therefore be easily imagined to confer an immunological and hence survival advantage to the organism. The co-segregation of immunogenicity of a variety of cancers with higher levels of expression of inducible hsp70, without any preceding change in the antigenic repertoire of the cancers, is a case in point (16,17). Conversely, the lack of such a signal may provide a mechanism for discrimination between the presence of antigen with and without `danger', as proposed by Matzinger (18). The quantities of HSP shown here to be necessary to stimulate APC in vitro are well within the range expected to be released locally as a result of cell lysis in vivo. Typically, 1 g of tissue yields ~30 µg gp96, 200 µg hsp70 and 400 µg hsp90. These recoveries are somewhere in the range of 25%. Thus 1 g of tissue contains ~2.5 mg HSP. Considering that the tissue lysis in vivo can be reasonably assumed to happen not in solution but in a semi-liquid physical state, lysis of as little as 1 mg of cells (~105–106 cells, depending on the cell type) will lead to release of ~2 µg HSP in a volume of ~1–2 µl or less. That is a concentration of 1–2 mg/ml—a higher concentration than that used in our studies in vitro. Considerations of quantity are therefore compatible with a role in vivo of HSP in activation of APC. Asea et al. (19) have reported recently that far lower concentrations of hsp70 than used in our studies are able to mediate stimulation of human monocytes. We are unable to detect any activity, either cytokine secretion or maturation of DC, at the concentrations of hsp70 used by Asea et al. The differences may be attributable to the differences in purity of our hsp70 preparations (see Fig. 2A
), possible differences between human and murine APC or functional differences between the APC populations used by us.
The HSP gp96 and hsp70 are not identical in their activity: gp96 induces MHC II and B7-2 but not B7-1, while hsp70 induces B7-1 but not MHC II nor B7-2. However, in view of the variability of B7-1 expression in our DC cultures (see Fig. 4 versus Fig. 6), the lack of effect of either HSP on B7-1 expression needs further examination. Neither HSP induces CD40, thus indicating that the maturation signal delivered by each is only partial. While these studies were under submission, Asea et al. (19) and Ohashi et al. (20) have reported on the ability of hsp70 and hsp60 respectively to stimulate monocytes or macrophages. Those results, together with our demonstration of release of gp96, hsp90, CRT and hsp70 by necrotic but not apoptotic death, and of the ability of gp96 and hsp70 to deliver a partial maturation signal to DC, support our original thesis (1,21,22) of a wider and general role for HSP as endogenous stress signals to APC.
Examination of the levels of cytokines released by macrophages or of the extent of induction of the maturation markers on DC by stimulation with HSP, shows that the HSP stimulate the APC to a modest degree, as compared with the stimulation conferred by LPS. For this reason, we have tested our observations repeatedly and have found them to be consistent. We wish to infer from this that the endogenous activators of DC (HSP in this instance) are much slower activators than external activators such as LPS for a physiological reason: the lower `specific activity' of endogenous signals allows for a more regulated activity, as the response to an internal signal might have to be far more modulated and more titratable, than that to an external signal. While our data show unambiguously the APC-stimulatory activity of HSP, they are silent on the question of other non-HSP activators of APC, which might be present in necrotic lysates. Other internal APC activators might indeed exist. Studies involving the APC-activating ability of necrotic lysates depleted of HSP should be revealing in this regard and are in progress.
The HSP are clearly more ancient and more ubiquitous than LPS, as even the earliest forms of life contain HSP, while LPS is unique to Gram-negative bacteria. We suggest that the HSP-mediated and LPS-mediated activation of APC represent utilization of similar mechanisms for similar objectives, although starting from different points. The mechanism of response to external danger may indeed be modeled on the more primitive mechanism of response to cellular disintegration that is usually signaled by the release of internal molecules such as HSP. Janeway has suggested that pattern recognition receptors present on APC serve to act as sentinels of the immune system against primordial non-self and its descendants (23). HSP are highly conserved between self and non-self organisms. In that light, the possibility that the ligands for the HSP which are responsible for the HSP–APC interaction may serve as pattern recognition receptors while at the same time acting as sentinels of internal danger is attractive, and helps reconcile the differences between the self/non-self and danger models of immune response.
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Acknowledgments |
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We thank Dr N. Qureshi for providing the LPS antagonist Rslp used in this study. We thank Maria Daou, Elishka Caneva and Diane Gran for the extensive endotoxin analysis of the protein preparations, and Jaqueline Beltran for excellent technical assistance. This work was supported by NIH grant CA64394, a Department of Defense (DARPA) grant (BAA96024) and a research agreement with Antigenics, in which one of us (P. K. S.) has a significant financial interest.
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Abbreviations |
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| APC antigen-presenting cell |
| CRT calreticulin |
| DC dendritic cell |
| GM-CSF granulocyte macrophage colony stimulating factor |
| HSP heat shock protein |
| LAL limulus amebocyte lysate |
| LBP LPS-binding protein |
| LPS lipopolysaccharide |
| TNF tumor necrosis factor |
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Notes |
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1 Present address: Apt A101 Osaki Houfu, Yamaguchi 747, Japan.
Transmitting editor: S. H. E. Kaufmann
Received 11 July 2000, accepted 21 July 2000.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Srivastava, P. K., Menoret, A., Basu, S., Binder R. J. and McQuade, K. L. 1998. Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity 8:657.[Web of Science][Medline]
- Janetzki, S., Palla, D., Rosenhauer, V., Lochs, H. and Srivastava, P. K. 2000. Immunization of cancer patients with autologous cancer-derived heat-shock protein gp96 preparations: a pilot study. Int. J. Cancer, in press.
-
Suto, R. and Srivastava, P. K. 1995. A mechanism for the specific immunogenicity of heat shock protein-chaperoned peptides. Science 269:1585.
[Abstract/Free Full Text] - Srivastava, P. K., Udono, H., Blachere, N. and Li, Z. 1994. Heat shock proteins transfer peptides during antigen processing and CTL priming. Immunogenetics 39:93.[Web of Science][Medline]
- Binder R., Han, D. and Srivastava, P. K. 2000. CD91: a receptor for the heat shock protein gp96. Nat. Immunol. 1:51.
- Srivastava, P. K. 1997. Purification of heat shock protein–peptide complexes for use in vaccination against cancers and intracellular pathogens. Methods Enzymol. 12:165.
- Lutz, M. B., Kukutsch, N., Ogilvie, A. L., Rossner, S., Koch, F., Romani, N. and Schuler, G. 1999. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J. Immunol. Methods 223:77.[Web of Science][Medline]
-
Dignam, J. D., Lebovitz R. M. and Roeder, R. G. 1983. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11:1475.
[Abstract/Free Full Text] - Schletter J., Heine, H., Ulmer, A. J. and Rietschel, E. T. 1995. Molecular mechanisms of endotoxin activity. Arch. Microbiol. 164:383.[Web of Science][Medline]
- Ulevitch, R. J. and Tobias, P. S. 1995. Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu. Rev. Immunol. 13:437.[Web of Science][Medline]
-
Henricson B. E., Perera, P. Y., Qureshi, N., Takayama K. and Vogel, S. N. 1992. Rhodopseudomonas sphaeroides lipid A derivatives block in vitro induction of tumor necrosis factor and endotoxin tolerance by smooth lipopolysaccharide and monophosphoryl lipid A. Infect. Immun. 60:4285.
[Abstract/Free Full Text] - Ghosh, S., May M. J. and Kopp, E. B. 1998. NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 16:225.[Web of Science][Medline]
-
Rescigno, M., Martino, M., Sutherland, C. L., Gold, M. R. and Ricciardi-Castagnoli, P. 1998. Dendritic cell survival and maturation are regulated by different signaling pathways. J. Exp. Med. 188:2175.
[Abstract/Free Full Text] - Gallucci, S., Lolkema, M. and Matzinger, P. 1999 Natural adjuvants: endogenous activators of dendritic cells. Nat. Med. 5:1249.[Web of Science][Medline]
-
Sauter, B., Albert, M. L., Francisco, L., Larsson, M., Somersan, S. and Bhardwaj, N. 2000. Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J. Exp. Med. 191:423.
[Abstract/Free Full Text] - Menoret, A., Patry, Y., Burg, C. and Le Pendu, J. 1995. Co-segregation of tumor immunogenicity with expression of inducible but not constitutive hsp70 in rat colon carcinomas. J. Immunol. 155:740.[Abstract]
- Melcher A, Todryk, S., Hardwick, N., Ford, M., Jacobson, M. and Vile, R. G. 1998. Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat. Med. 5:581.
- Fuchs, E. J. and Matzinger, P. 1996. Is cancer dangerous to the immune system? Semin. Immunol. 8:271.[Medline]
- Asea, A., Kraeft, S. K., Kurt-Jones, E. A., Stevenson, M. A., Chen, L. B., Finberg, R. W. and Calderwood, S. K. 2000. Hsp70 stimulates cytokine production through a CD14-dependent pathway, demonstrating its dual role as a chaperone and cytokine. Nat. Med. 6:435.[Web of Science][Medline]
-
Ohashi, K., Burkart, V., Flohe, S. and Kolb, H. 2000. Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J. Immunol. 164:558.
[Abstract/Free Full Text] - Basu, S., Suto, R., Binder, R. and Srivastava, P. K. 1998. Heat shock proteins as novel mediators of cytokine secretion by macrophages. Cell Stress & Chaperones 3:11.
-
Basu, S., Binder, R., Suto, R., Anderson, K. M. and Srivastava, P. K. 2000. Mammalian heat shock proteins signal cell death through activation of the NFB pathway in antigen presenting cells. FASEB J. 14:A945.
- Medzhitov, R. and Janeway, C. A., Jr. 1997. Innate immunity: the virtues of a nonclonal system of recognition. Cell 91:295.[Web of Science][Medline]
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S. Lehnardt, E. Schott, T. Trimbuch, D. Laubisch, C. Krueger, G. Wulczyn, R. Nitsch, and J. R. Weber A Vicious Cycle Involving Release of Heat Shock Protein 60 from Injured Cells and Activation of Toll-Like Receptor 4 Mediates Neurodegeneration in the CNS J. Neurosci., March 5, 2008; 28(10): 2320 - 2331. [Abstract] [Full Text] [PDF]
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|
|
|
J. H. H. Williams and H. E. Ireland Sensing danger--Hsp72 and HMGB1 as candidate signals J. Leukoc. Biol., March 1, 2008; 83(3): 489 - 492. [Abstract] [Full Text] [PDF]
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J. Robert, T. Ramanayake, G. D. Maniero, H. Morales, and A. S. Chida Phylogenetic Conservation of Glycoprotein 96 Ability to Interact with CD91 and Facilitate Antigen Cross-Presentation J. Immunol., March 1, 2008; 180(5): 3176 - 3182. [Abstract] [Full Text] [PDF]
|
|
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R. M. Srivastava, C. Varalakshmi, and A. Khar The Ischemia-Responsive Protein 94 (Irp94) Activates Dendritic Cells through NK Cell Receptor Protein-2/NK Group 2 Member D (NKR-P2/NKG2D) Leading to Their Maturation J. Immunol., January 15, 2008; 180(2): 1117 - 1130. [Abstract] [Full Text] [PDF]
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 |
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 F. D. Khan, P. M. Vyas, A. A. Gaspari, and C. K. Svensson Effect of Arylhydroxylamine Metabolites of Sulfamethoxazole and Dapsone on Stress Signal Expression in Human Keratinocytes J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 771 - 777. [Abstract] [Full Text] [PDF]
|
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M. A. Chase, D. S. Wheeler, K. M. Lierl, V. S. Hughes, H. R. Wong, and K. Page Hsp72 Induces Inflammation and Regulates Cytokine Production in Airway Epithelium through a TLR4- and NF-{kappa}B-Dependent Mechanism J. Immunol., November 1, 2007; 179(9): 6318 - 6324. [Abstract] [Full Text] [PDF]
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H. Bendz, S. C. Ruhland, M. J. Pandya, O. Hainzl, S. Riegelsberger, C. Brauchle, M. P. Mayer, J. Buchner, R. D. Issels, and E. Noessner Human Heat Shock Protein 70 Enhances Tumor Antigen Presentation through Complex Formation and Intracellular Antigen Delivery without Innate Immune Signaling J. Biol. Chem., October 26, 2007; 282(43): 31688 - 31702. [Abstract] [Full Text] [PDF]
|
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 |
|
 M. Whitham, S. J. Laing, A. Jackson, N. Maassen, and N. P. Walsh Effect of exercise with and without a thermal clamp on the plasma heat shock protein 72 response J Appl Physiol, October 1, 2007; 103(4): 1251 - 1256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Markiewski and J. D. Lambris The Role of Complement in Inflammatory Diseases From Behind the Scenes into the Spotlight Am. J. Pathol., September 1, 2007; 171(3): 715 - 727. [Abstract] [Full Text] [PDF]
|
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|
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A. Mukhopadhaya, J. Mendecki, X. Dong, L. Liu, S. Kalnicki, M. Garg, A. Alfieri, and C. Guha Localized Hyperthermia Combined with Intratumoral Dendritic Cells Induces Systemic Antitumor Immunity Cancer Res., August 15, 2007; 67(16): 7798 - 7806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Johansson, L. Walther-Jallow, A. Smed-Sorensen, and A.-L. Spetz Triggering of Dendritic Cell Responses after Exposure to Activated, but Not Resting, Apoptotic PBMCs J. Immunol., August 1, 2007; 179(3): 1711 - 1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kurotaki, Y. Tamura, G. Ueda, J. Oura, G. Kutomi, Y. Hirohashi, H. Sahara, T. Torigoe, H. Hiratsuka, H. Sunakawa, et al. Efficient Cross-Presentation by Heat Shock Protein 90-Peptide Complex-Loaded Dendritic Cells via an Endosomal Pathway J. Immunol., August 1, 2007; 179(3): 1803 - 1813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Deocharan, Z. Zhou, K. Antar, L. Siconolfi-Baez, R. H. Angeletti, J. Hardin, and C. Putterman {alpha}-Actinin Immunization Elicits Anti-Chromatin Autoimmunity in Nonautoimmune Mice J. Immunol., July 15, 2007; 179(2): 1313 - 1321. [Abstract] [Full Text] [PDF]
|
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|
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L.-P. Erwig and P. M. Henson Immunological Consequences of Apoptotic Cell Phagocytosis Am. J. Pathol., July 1, 2007; 171(1): 2 - 8. [Abstract] [Full Text] [PDF]
|
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|
|
U. Koedel, U. M. Merbt, C. Schmidt, B. Angele, B. Popp, H. Wagner, H.-W. Pfister, and C. J. Kirschning Acute Brain Injury Triggers MyD88-Dependent, TLR2/4-Independent Inflammatory Responses Am. J. Pathol., July 1, 2007; 171(1): 200 - 213. [Abstract] [Full Text] [PDF]
|
|
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|
|
|
J. M. Han, S. G. Park, B. Liu, B.-J. Park, J. Y. Kim, C. H. Jin, Y. W. Song, Z. Li, and S. Kim Aminoacyl-tRNA Synthetase-Interacting Multifunctional Protein 1/p43 Controls Endoplasmic Reticulum Retention of Heat Shock Protein gp96: Its Pathological Implications in Lupus-Like Autoimmune Diseases Am. J. Pathol., June 1, 2007; 170(6): 2042 - 2054. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
R. Spisek, A. Charalambous, A. Mazumder, D. H. Vesole, S. Jagannath, and M. V. Dhodapkar Bortezomib enhances dendritic cell (DC) mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: therapeutic implications Blood, June 1, 2007; 109(11): 4839 - 4845. [Abstract] [Full Text] [PDF]
|
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T. S. Griffith, H. Kazama, R. L. VanOosten, J. K. Earle Jr., J. M. Herndon, D. R. Green, and T. A. Ferguson Apoptotic Cells Induce Tolerance by Generating Helpless CD8+ T Cells That Produce TRAIL J. Immunol., March 1, 2007; 178(5): 2679 - 2687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Beltran, A. K. Ghosh, and S. Basu Immunotherapy of Tumors with Neuroimmune Ligand Capsaicin J. Immunol., March 1, 2007; 178(5): 3260 - 3264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gamrekelashvili, C. Kruger, R. von Wasielewski, M. Hoffmann, K. M. Huster, D. H. Busch, M. P. Manns, F. Korangy, and T. F. Greten Necrotic Tumor Cell Death In Vivo Impairs Tumor-Specific Immune Responses J. Immunol., February 1, 2007; 178(3): 1573 - 1580. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pido-Lopez, T. Whittall, Y. Wang, L. A. Bergmeier, K. Babaahmady, M. Singh, and T. Lehner Stimulation of Cell Surface CCR5 and CD40 Molecules by Their Ligands or by HSP70 Up-Regulates APOBEC3G Expression in CD4+ T Cells and Dendritic Cells J. Immunol., February 1, 2007; 178(3): 1671 - 1679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tsung, N. Zheng, G. Jeyabalan, K. Izuishi, J. R. Klune, D. A. Geller, M. T. Lotze, L. Lu, and T. R. Billiar Increasing numbers of hepatic dendritic cells promote HMGB1-mediated ischemia-reperfusion injury J. Leukoc. Biol., January 1, 2007; 81(1): 119 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, A. Dutuor, L. Tao, X. Fu, and X. Zhang Virotherapy with a Type 2 Herpes Simplex Virus-Derived Oncolytic Virus Induces Potent Antitumor Immunity against Neuroblastoma Clin. Cancer Res., January 1, 2007; 13(1): 316 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Mambula and S. K. Calderwood Heat Shock Protein 70 Is Secreted from Tumor Cells by a Nonclassical Pathway Involving Lysosomal Endosomes J. Immunol., December 1, 2006; 177(11): 7849 - 7857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Direskeneli Autoimmunity vs autoinflammation in Behcet's disease: do we oversimplify a complex disorder? Rheumatology, December 1, 2006; 45(12): 1461 - 1465. [Full Text] [PDF]
|
|
|
|
|
|
B. Liu, Y. Yang, J. Dai, R. Medzhitov, M. A. Freudenberg, P. L. Zhang, and Z. Li TLR4 Up-Regulation at Protein or Gene Level Is Pathogenic for Lupus-Like Autoimmune Disease J. Immunol., November 15, 2006; 177(10): 6880 - 6888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Aneja, K. Odoms, K. Dunsmore, T. P. Shanley, and H. R. Wong Extracellular Heat Shock Protein-70 Induces Endotoxin Tolerance in THP-1 Cells J. Immunol., November 15, 2006; 177(10): 7184 - 7192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Telusma, S. Datta, I. Mihajlov, W. Ma, J. Li, H. Yang, W. Newman, B. T. Messmer, B. Minev, I. G. H. Schmidt-Wolf, et al. Dendritic cell activating peptides induce distinct cytokine profiles Int. Immunol., November 1, 2006; 18(11): 1563 - 1573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Ganter, L. B. Ware, M. Howard, J. Roux, B. Gartland, M. A. Matthay, M. Fleshner, and J.-F. Pittet Extracellular heat shock protein 72 is a marker of the stress protein response in acute lung injury Am J Physiol Lung Cell Mol Physiol, September 1, 2006; 291(3): L354 - L361. [Abstract] [Full Text] [PDF]
|
|
|
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|
|
T. Warger, N. Hilf, G. Rechtsteiner, P. Haselmayer, D. M. Carrick, H. Jonuleit, P. von Landenberg, H.-G. Rammensee, C. V. Nicchitta, M. P. Radsak, et al. Interaction of TLR2 and TLR4 Ligands with the N-terminal Domain of Gp96 Amplifies Innate and Adaptive Immune Responses J. Biol. Chem., August 11, 2006; 281(32): 22545 - 22553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Y. Wang, H. Arnouk, X. Chen, L. Kazim, E. A. Repasky, and J. R. Subjeck Extracellular Targeting of Endoplasmic Reticulum Chaperone Glucose-Regulated Protein 170 Enhances Tumor Immunity to a Poorly Immunogenic Melanoma J. Immunol., August 1, 2006; 177(3): 1543 - 1551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Flechtner, K. P. Cohane, S. Mehta, P. Slusarewicz, A. K. Leonard, B. H. Barber, D. L. Levey, and S. Andjelic High-Affinity Interactions between Peptides and Heat Shock Protein 70 Augment CD8+ T Lymphocyte Immune Responses J. Immunol., July 15, 2006; 177(2): 1017 - 1027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Biswas, U. Sriram, B. Ciric, O. Ostrovsky, S. Gallucci, and Y. Argon The N-terminal fragment of GRP94 is sufficient for peptide presentation via professional antigen-presenting cells Int. Immunol., July 1, 2006; 18(7): 1147 - 1157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Johnson and M. Fleshner Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72 J. Leukoc. Biol., March 1, 2006; 79(3): 425 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wang, J. T. Kovalchin, P. Muhlenkamp, and R. Y. Chandawarkar Exogenous heat shock protein 70 binds macrophage lipid raft microdomain and stimulates phagocytosis, processing, and MHC-II presentation of antigens Blood, February 15, 2006; 107(4): 1636 - 1642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-E. Park, J. Facciponte, X. Chen, I. MacDonald, E. A. Repasky, M. H. Manjili, X.-Y. Wang, and J. R. Subjeck Chaperoning Function of Stress Protein grp170, a Member of the hsp70 Superfamily, Is Responsible for its Immunoadjuvant Activity Cancer Res., January 15, 2006; 66(2): 1161 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Preynat-Seauve, P. Schuler, E. Contassot, F. Beermann, B. Huard, and L. E. French Tumor-Infiltrating Dendritic Cells Are Potent Antigen-Presenting Cells Able to Activate T Cells and Mediate Tumor Rejection J. Immunol., January 1, 2006; 176(1): 61 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. de Bouteiller, E. Merck, U. A. Hasan, S. Hubac, B. Benguigui, G. Trinchieri, E. E. M. Bates, and C. Caux Recognition of Double-stranded RNA by Human Toll-like Receptor 3 and Downstream Receptor Signaling Requires Multimerization and an Acidic pH J. Biol. Chem., November 18, 2005; 280(46): 38133 - 38145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L. Vega and A. De Maio Increase in Phagocytosis after Geldanamycin Treatment or Heat Shock: Role of Heat Shock Proteins J. Immunol., October 15, 2005; 175(8): 5280 - 5287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Massa, C. Melani, and M. P. Colombo Chaperon and Adjuvant Activity of hsp70: Different Natural Killer Requirement for Cross-Priming of Chaperoned and Bystander Antigens Cancer Res., September 1, 2005; 65(17): 7942 - 7949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Pritchard, Z. Li, and E. A. Repasky Nitric oxide production is regulated by fever-range thermal stimulation of murine macrophages J. Leukoc. Biol., September 1, 2005; 78(3): 630 - 638. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Quintana and I. R. Cohen Heat Shock Proteins as Endogenous Adjuvants in Sterile and Septic Inflammation J. Immunol., September 1, 2005; 175(5): 2777 - 2782. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Bausero, R. Gastpar, G. Multhoff, and A. Asea Alternative Mechanism by which IFN-{gamma} Enhances Tumor Recognition: Active Release of Heat Shock Protein 72 J. Immunol., September 1, 2005; 175(5): 2900 - 2912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Vermaelen and R. Pauwels Pulmonary Dendritic Cells Am. J. Respir. Crit. Care Med., September 1, 2005; 172(5): 530 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Clayton, A. Turkes, H. Navabi, M. D. Mason, and Z. Tabi Induction of heat shock proteins in B-cell exosomes J. Cell Sci., August 15, 2005; 118(16): 3631 - 3638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A Wallet, P. Sen, and R. Tisch Immunoregulation of Dendritic Cells Clin. Med. Res., August 1, 2005; 3(3): 166 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Correale*, M. G. Cusi, M. T. Del Vecchio, A. Aquino, S. Prete, K. Y. Tsang, L. Micheli, C. Nencini, M. La Placa*, F. Montagnani*, et al. Dendritic Cell-Mediated Cross-Presentation of Antigens Derived from Colon Carcinoma Cells Exposed to a Highly Cytotoxic Multidrug Regimen with Gemcitabine, Oxaliplatin, 5-Fluorouracil, and Leucovorin, Elicits a Powerful Human Antigen-Specific CTL Response with Antitumor Activity in Vitro J. Immunol., July 15, 2005; 175(2): 820 - 828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. W. Graner and D. D. Bigner Chaperone proteins and brain tumors: Potential targets and possible therapeutics Neuro-oncol, July 1, 2005; 7(3): 260 - 278. [Abstract] [PDF]
|
|
|
|
|
|
A. Kebba, J. Stebbing, S. Rowland, R. Ingram, J. Agaba, S. Patterson, P. Kaleebu, N. Imami, and F. Gotch Expression of the common heat-shock protein receptor CD91 is increased on monocytes of exposed yet HIV-1-seronegative subjects J. Leukoc. Biol., July 1, 2005; 78(1): 37 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Li, Y. Qiao, B. Liu, E. J. Laska, P. Chakravarthi, J. M. Kulko, R. D. Bona, M. Fang, U. Hegde, V. Moyo, et al. Combination of Imatinib Mesylate with Autologous Leukocyte-Derived Heat Shock Protein and Chronic Myelogenous Leukemia Clin. Cancer Res., June 15, 2005; 11(12): 4460 - 4468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Bulut, K. S. Michelsen, L. Hayrapetian, Y. Naiki, R. Spallek, M. Singh, and M. Arditi Mycobacterium Tuberculosis Heat Shock Proteins Use Diverse Toll-like Receptor Pathways to Activate Pro-inflammatory Signals J. Biol. Chem., June 3, 2005; 280(22): 20961 - 20967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Yu. Nikitina, S. A. Desai, X. Zhao, W. Song, A. Z. Luo, R. D. Gangula, K. M. Slawin, and D. M. Spencer Versatile Prostate Cancer Treatment with Inducible Caspase and Interleukin-12 Cancer Res., May 15, 2005; 65(10): 4309 - 4319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pilla, P. Squarcina, J. Coppa, V. Mazzaferro, V. Huber, D. Pende, C. Maccalli, G. Sovena, L. Mariani, C. Castelli, et al. Natural Killer and NK-Like T-Cell Activation in Colorectal Carcinoma Patients Treated with Autologous Tumor-Derived Heat Shock Protein 96 Cancer Res., May 1, 2005; 65(9): 3942 - 3949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Basu and P. Srivastava Immunological role of neuronal receptor vanilloid receptor 1 expressed on dendritic cells PNAS, April 5, 2005; 102(14): 5120 - 5125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Demaria, F. R. Santori, B. Ng, L. Liebes, S. C. Formenti, and S. Vukmanovic Select forms of tumor cell apoptosis induce dendritic cell maturation J. Leukoc. Biol., March 1, 2005; 77(3): 361 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Rharbaoui, D. Bruder, M. Vidakovic, T. Ebensen, J. Buer, and C. A. Guzman Characterization of a B220+ Lymphoid Cell Subpopulation with Immune Modulatory Functions in Nasal-Associated Lymphoid Tissues J. Immunol., February 1, 2005; 174(3): 1317 - 1324. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Prasad, K. J. Farrand, S. A. Matthews, J. H. Chang, R. S. McHugh, and F. Ronchese Dendritic Cells Loaded with Stressed Tumor Cells Elicit Long-Lasting Protective Tumor Immunity in Mice Depleted of CD4+CD25+ Regulatory T Cells J. Immunol., January 1, 2005; 174(1): 90 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Berwin, Y. Delneste, R. V. Lovingood, S. R. Post, and S. V. Pizzo SREC-I, a Type F Scavenger Receptor, Is an Endocytic Receptor for Calreticulin J. Biol. Chem., December 3, 2004; 279(49): 51250 - 51257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Osterloh, F. Meier-Stiegen, A. Veit, B. Fleischer, A. von Bonin, and M. Breloer Lipopolysaccharide-free Heat Shock Protein 60 Activates T Cells J. Biol. Chem., November 12, 2004; 279(46): 47906 - 47911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Lewis Therapeutic cancer vaccines: Using unique antigens PNAS, October 5, 2004; 101(suppl_2): 14653 - 14656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tang, H. B. Rossiter, P. D. Wagner, and E. C. Breen Lung-targeted VEGF inactivation leads to an emphysema phenotype in mice J Appl Physiol, October 1, 2004; 97(4): 1559 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ren, R. Strube, X. Zhang, S.-Y. Chen, and X. F. Huang Potent Tumor-Specific Immunity Induced by an In vivo Heat Shock Protein-Suicide Gene-Based Tumor Vaccine Cancer Res., September 15, 2004; 64(18): 6645 - 6651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Nagy, M. Barcza, N. Gonchoroff, P. E. Phillips, and A. Perl Nitric Oxide-Dependent Mitochondrial Biogenesis Generates Ca2+ Signaling Profile of Lupus T Cells J. Immunol., September 15, 2004; 173(6): 3676 - 3683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-F. Tsan and B. Gao Endogenous ligands of Toll-like receptors J. Leukoc. Biol., September 1, 2004; 76(3): 514 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. SenGupta, P. J. Norris, T. J. Suscovich, M. Hassan-Zahraee, H. F. Moffett, A. Trocha, R. Draenert, P. J. R. Goulder, R. J. Binder, D. L. Levey, et al. Heat Shock Protein-Mediated Cross-Presentation of Exogenous HIV Antigen on HLA Class I and Class II J. Immunol., August 1, 2004; 173(3): 1987 - 1993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Messmer, H. Yang, G. Telusma, F. Knoll, J. Li, B. Messmer, K. J. Tracey, and N. Chiorazzi High Mobility Group Box Protein 1: An Endogenous Signal for Dendritic Cell Maturation and Th1 Polarization J. Immunol., July 1, 2004; 173(1): 307 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. H. Doody, J. T. Kovalchin, M. A. Mihalyo, A. T. Hagymasi, C. G. Drake, and A. J. Adler Glycoprotein 96 Can Chaperone Both MHC Class I- and Class II-Restricted Epitopes for In Vivo Presentation, but Selectively Primes CD8+ T Cell Effector Function J. Immunol., May 15, 2004; 172(10): 6087 - 6092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Jones, D. P. Ankeny, Z. Guan, V. McGaughy, L. C. Fisher, D. M. Basso, and P. G. Popovich Passive or Active Immunization with Myelin Basic Protein Impairs Neurological Function and Exacerbates Neuropathology after Spinal Cord Injury in Rats J. Neurosci., April 14, 2004; 24(15): 3752 - 3761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-F. Tsan and B. Gao Cytokine function of heat shock proteins Am J Physiol Cell Physiol, April 1, 2004; 286(4): C739 - C744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Baker-LePain, M. Sarzotti, and C. V. Nicchitta Glucose-Regulated Protein 94/Glycoprotein 96 Elicits Bystander Activation of CD4+ T Cell Th1 Cytokine Production In Vivo J. Immunol., April 1, 2004; 172(7): 4195 - 4203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kariko, H. Ni, J. Capodici, M. Lamphier, and D. Weissman mRNA Is an Endogenous Ligand for Toll-like Receptor 3 J. Biol. Chem., March 26, 2004; 279(13): 12542 - 12550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Massa, C. Guiducci, I. Arioli, M. Parenza, M. P. Colombo, and C. Melani Enhanced Efficacy of Tumor Cell Vaccines Transfected with Secretable hsp70 Cancer Res., February 15, 2004; 64(4): 1502 - 1508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Liu, J. Dai, H. Zheng, D. Stoilova, S. Sun, and Z. Li Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases PNAS, December 23, 2003; 100(26): 15824 - 15829. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. F. Huang, W. Ren, L. Rollins, P. Pittman, M. Shah, L. Shen, Q. Gu, R. Strube, F. Hu, and S.-Y. Chen A Broadly Applicable, Personalized Heat Shock Protein-Mediated Oncolytic Tumor Vaccine Cancer Res., November 1, 2003; 63(21): 7321 - 7329. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Manjili, X.-Y. Wang, X. Chen, T. Martin, E. A. Repasky, R. Henderson, and J. R. Subjeck HSP110-HER2/neu Chaperone Complex Vaccine Induces Protective Immunity Against Spontaneous Mammary Tumors in HER-2/neu Transgenic Mice J. Immunol., October 15, 2003; 171(8): 4054 - 4061. [Abstract] [Full Text] [PDF]
|
|
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 |
|
 S. Shi, C. Nathan, D. Schnappinger, J. Drenkow, M. Fuortes, E. Block, A. Ding, T. R. Gingeras, G. Schoolnik, S. Akira, et al. MyD88 Primes Macrophages for Full-Scale Activation by Interferon-{gamma} yet Mediates Few Responses to Mycobacterium tuberculosis J. Exp. Med., October 6, 2003; 198(7): 987 - 997. [Abstract] [Full Text] [PDF]
|
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|
|
N. Jiang, C. F. Reich III, and D. S. Pisetsky Role of macrophages in the generation of circulating blood nucleosomes from dead and dying cells Blood, September 15, 2003; 102(6): 2243 - 2250. [Abstract] [Full Text] [PDF]
|
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|
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S. Basu and P. K. Srivastava Fever-like temperature induces maturation of dendritic cells through induction of hsp90 Int. Immunol., September 1, 2003; 15(9): 1053 - 1061. [Abstract] [Full Text] [PDF]
|
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R. C. Reed, B. Berwin, J. P. Baker, and C. V. Nicchitta GRP94/gp96 Elicits ERK Activation in Murine Macrophages: A ROLE FOR ENDOTOXIN CONTAMINATION IN NF-{kappa}B ACTIVATION AND NITRIC OXIDE PRODUCTION J. Biol. Chem., August 22, 2003; 278(34): 31853 - 31860. [Abstract] [Full Text] [PDF]
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A. N. Rad, G. Pollara, S. M. A. Sohaib, C. Chiang, B. M. Chain, and D. R. Katz The Differential Influence of Allogeneic Tumor Cell Death via DNA Damage on Dendritic Cell Maturation and Antigen Presentation Cancer Res., August 15, 2003; 63(16): 5143 - 5150. [Abstract] [Full Text] [PDF]
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Y. Zeng, H. Feng, M. W. Graner, and E. Katsanis Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity Blood, June 1, 2003; 101(11): 4485 - 4491. [Abstract] [Full Text] [PDF]
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X.-Y. Wang, X. Chen, M. H. Manjili, E. Repasky, R. Henderson, and J. R. Subjeck Targeted Immunotherapy Using Reconstituted Chaperone Complexes of Heat Shock Protein 110 and Melanoma-associated Antigen gp100 Cancer Res., May 15, 2003; 63(10): 2553 - 2560. [Abstract] [Full Text] [PDF]
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J. Stebbing, B. Gazzard, L. Kim, S. Portsmouth, A. Wildfire, I. Teo, M. Nelson, M. Bower, F. Gotch, S. Shaunak, et al. The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1-infected "true" long-term nonprogressors Blood, May 15, 2003; 101(10): 4000 - 4004. [Abstract] [Full Text] [PDF]
|
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M. P. Radsak, N. Hilf, H. Singh-Jasuja, S. Braedel, P. Brossart, H.-G. Rammensee, and H. Schild The heat shock protein Gp96 binds to human neutrophils and monocytes and stimulates effector functions Blood, April 1, 2003; 101(7): 2810 - 2815. [Abstract] [Full Text] [PDF]
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S. B. Flohe, J. Bruggemann, S. Lendemans, M. Nikulina, G. Meierhoff, S. Flohe, and H. Kolb Human Heat Shock Protein 60 Induces Maturation of Dendritic Cells Versus a Th1-Promoting Phenotype J. Immunol., March 1, 2003; 170(5): 2340 - 2348. [Abstract] [Full Text] [PDF]
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