International Immunology, Vol. 12, No. 6, 887-897,
June 2000
© 2000 Japanese Society for Immunology
In vitro and in vivo macrophage function can occur independently of SLP-76
1 Department of Physiology and Biophysics,
2 Department of Internal Medicine,
3 Interdisciplinary Immunology Program,
4 Inflammation Program,
5 Department of Microbiology, University of Iowa College of Medicine and Veterans Administration Medical Center, Iowa City, IA 52242, USA
Correspondence to: G. A. Koretzky, University of Pennsylvania, The Leonard and Madlyn Abramson Family Cancer Research Institute, 421 Curie Boulevard, 415 BRB II/III, Philadelphia, PA 19104-6160, USA
Expression of SH2 domain-containing leukocyte-specific phosphoprotein of 76 kDa (SLP-76), a hematopoietic cell-specific adapter protein, is required to couple Syk family tyrosine kinase activation to downstream mediators such as phospholipase C (PLC)-
following TCR, platelet collagen receptor and mast cell Fc
R stimulation. In addition to T cells, mast cells and platelets, SLP-76 is expressed in monocytes and macrophages. To determine the role of SLP-76 in FcR-stimulated signaling pathways in macrophages, we examined cultured bone marrow-derived macrophages (BMM) from SLP-76–/– and wild-type mice. In this study, we show that FcR cross-linking rapidly induces tyrosine phosphorylation of SLP-76 in wild-type BMM. Surprisingly, however, BMM from SLP-76–/– mice activate ERK2 and phosphorylate PLC-2 following FcR ligation. Furthermore, SLP-76–/– BMM display normal FcR-dependent phagocytic function and reactive oxygen intermediate production. SLP-76–/– and SLP-76+/+ BMM secrete comparable levels of IL-12 in response to lipopolysaccharide and IFN-. To examine macrophage function in vivo, SLP-76–/– mice were challenged i.v. with Listeria monocytogenes. SLP-76–/– mice survive and efficiently contain the acute phase of infection similar to wild-type mice but exhibit a stable chronic infection attributed to the lack of mature T cells. These data show that, although SLP-76 is required to couple Syk family PTK activity to downstream mediators and effector functions in FcR-induced pathways in some cell types, activation of FcR-dependent pathways occurs independently of SLP-76 in BMM.
Keywords: Fc receptors, monocytes/macrophages, phagocytosis, signal transduction
Transmitting editor: J. Bluestone
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Yamasaki, M. Takase-Utsugi, E. Ishikawa, M. Sakuma, K. Nishida, T. Saito, and O. Kanagawa Selective impairment of Fc{varepsilon}RI-mediated allergic reaction in Gads-deficient mice Int. Immunol., October 1, 2008; 20(10): 1289 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Clemens, L. E. Lenox, T. Kambayashi, N. Bezman, J. S. Maltzman, K. E. Nichols, and G. A. Koretzky Loss of SLP-76 Expression within Myeloid Cells Confers Resistance to Neutrophil-Mediated Tissue Damage while Maintaining Effective Bacterial Killing J. Immunol., April 1, 2007; 178(7): 4606 - 4614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Luckashenak, R. L. Ryszkiewicz, K. D. Ramsey, and J. L. Clements The Src Homology 2 Domain-Containing Leukocyte Protein of 76-kDa Adaptor Links Integrin Ligation with p44/42 MAPK Phosphorylation and Podosome Distribution in Murine Dendritic Cells J. Immunol., October 15, 2006; 177(8): 5177 - 5185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-X. Zong, D. Ditsworth, D. E. Bauer, Z.-Q. Wang, and C. B. Thompson Alkylating DNA damage stimulates a regulated form of necrotic cell death Genes & Dev., June 1, 2004; 18(11): 1272 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Nichols, K. Haines, P. S. Myung, S. Newbrough, E. Myers, H. Jumaa, D. J. Shedlock, H. Shen, and G. A. Koretzky Macrophage activation and Fc{gamma} receptor-mediated signaling do not require expression of the SLP-76 and SLP-65 adaptors J. Leukoc. Biol., March 1, 2004; 75(3): 541 - 552. [Abstract] [Full Text] [PDF]
|
|