International Immunology, Vol. 11, No. 7, 1075-1083,
July 1999
© 1999 Japanese Society for Immunology
STAT1 activation during monocyte to macrophage maturation: role of adhesion molecules
1 Laboratory of Virology,
2 Laboratory of Immunology, and
3 Laboratory of Hematology and Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
Correspondence to: A. Battistini and E. Coccia
Human monocytes isolated from peripheral blood of healthy donors show a time-dependent differentiation into macrophages upon in vitro cultivation, closely mimicking their in vivo migration and maturation into extravascular tissues. The mediator(s) of this maturation process has not been yet defined. We investigated the involvement of signal transducers and activators of transcription (STAT) factors in this phenomenon and reported the specific, time-dependent, activation of STAT1 protein starting at day 0/1 of cultivation and maximally expressed at day 5. STAT1 activity was evident on the STAT binding sequences (SBE) present in the promoters of genes which are up-regulated during monocyte to macrophage maturation such as Fc
RI and ICAM-1, and in the promoter of the transcription factor IFN regulatory factor-1. Moreover, the effect of cell adhesion to fibronectin or laminin was studied to investigate mechanisms involved in STAT1 activation. Compared with monocytes adherent on plastic surfaces, freshly isolated cells allowed to adhere either to fibronectin- or laminin-coated flasks exhibited an increased STAT1 binding activity both in control and in IFN--treated cells. The molecular events leading to enhanced STAT1 activation and cytokine responsiveness concerned both Y701 and S727 STAT1 phosphorylation. Exogenous addition of transforming growth factor-ß, which exerts an inhibitory effect on some monocytic differentiation markers, inhibited macrophage maturation, integrin expression and STAT1 binding activity. Taken together these results indicate that STAT1 plays a pivotal role in the differentiation/maturation process of monocytes as an early transcription factor initially activated by adherence and then able to modulate the expression of functional genes, such as ICAM-1 and FcRI.
Keywords: cellular differentiation, signal transduction
Transmitting editor: T. Taniguchi
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Agrawal, M. Febbraio, E. Podrez, M. K. Cathcart, G. R. Stark, and G. M. Chisolm Signal Transducer and Activator of Transcription 1 Is Required for Optimal Foam Cell Formation and Atherosclerotic Lesion Development Circulation, June 12, 2007; 115(23): 2939 - 2947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Singhal, A. Jaiswal, V. K. Arora, and H. K. Prasad Modulation of Gamma Interferon Receptor 1 by Mycobacterium tuberculosis: a Potential Immune Response Evasive Mechanism Infect. Immun., May 1, 2007; 75(5): 2500 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Moriguchi, M. Hamada, N. Morito, T. Terunuma, K. Hasegawa, C. Zhang, T. Yokomizo, R. Esaki, E. Kuroda, K. Yoh, et al. MafB Is Essential for Renal Development and F4/80 Expression in Macrophages Mol. Cell. Biol., August 1, 2006; 26(15): 5715 - 5727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Pick, M. Rawat, D. Arad, J. Lan, J. Fan, A. S. Kende, and Y. Av-Gay In vitro properties of antimicrobial bromotyrosine alkaloids. J. Med. Microbiol., April 1, 2006; 55(Pt 4): 407 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Burger, N. Molnarfi, L. Gruaz, and J.-M. Dayer Differential Induction of IL-1{beta} and TNF by CD40 Ligand or Cellular Contact with Stimulated T Cells Depends on the Maturation Stage of Human Monocytes J. Immunol., July 15, 2004; 173(2): 1292 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-F. Petit-Bertron, C. Fitting, J.-M. Cavaillon, and M. Adib-Conquy Adherence influences monocyte responsiveness to interleukin-10 J. Leukoc. Biol., January 1, 2003; 73(1): 145 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Federico, Z. Percario, E. Olivetta, G. Fiorucci, C. Muratori, A. Micheli, G. Romeo, and E. Affabris HIV-1 Nef activates STAT1 in human monocytes/macrophages through the release of soluble factors Blood, November 1, 2001; 98(9): 2752 - 2761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. TEGEDER, J. PFEILSCHIFTER, and G. GEISSLINGER Cyclooxygenase-independent actions of cyclooxygenase inhibitors FASEB J, October 1, 2001; 15(12): 2057 - 2072. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Grewal, E. Priceputu, J. Davignon, and L. Bernier Identification of a {{gamma}}-Interferon-Responsive Element in the Promoter of the Human Macrophage Scavenger Receptor A Gene Arterioscler. Thromb. Vasc. Biol., May 1, 2001; 21(5): 825 - 831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Coccia, E. Stellacci, G. Marziali, G. Weiss, and A. Battistini IFN-{gamma} and IL-4 differently regulate inducible NO synthase gene expression through IRF-1 modulation Int. Immunol., July 1, 2000; 12(7): 977 - 985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Roy, M. Audette, and M. J. Tremblay Intercellular Adhesion Molecule-1 (ICAM-1) Gene Expression in Human T Cells Is Regulated by Phosphotyrosyl Phosphatase Activity. INVOLVEMENT OF NF-kappa B, Ets, AND PALINDROMIC INTERFERON-gamma -RESPONSIVE ELEMENT-BINDING SITES J. Biol. Chem., April 27, 2001; 276(18): 14553 - 14561. [Abstract] [Full Text] [PDF]
|
|