Human monocyte binding to fibronectin enhances IFN-γ-induced early signaling events

James B. McCarthy, Bina V. Vachhani, Sharon M. Wahl, David S. Finbloom, Gerald M. Feldman

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Leukocyte integrins are fundamentally important in modulating adhesion to extracellular matrix components and to other cells. This integrin-mediated adhesion controls leukocyte arrest and extravasation during the onset of inflammatory responses. Moreover, integrin-ligand interactions trigger signaling pathways that may influence leukocyte phenotype and function at sites of inflammation. In the current studies, we evaluated the combinatorial effects of monocyte adhesion and IFN-γ on intracellular signaling pathways. IFN-γ triggers a well-defined signal transduction pathway, which although not directly stimulated by monocyte adherence to fibronectin or arginine-glycine-aspartate (RGD)-coated substrata, was enhanced significantly in these matrix-adherent cells. Compared with monocytes in suspension or adherent on plastic surfaces, monocytes adherent to fibronectin or RGD exhibited a greater than threefold increase in steady state levels of IFN-γ-induced mRNA for the high affinity FcγRI receptor. By electrophoretic mobility shift assays, this increase in mRNA was associated with a 5- to 10-fold increase in the STAT1-containing DNA-binding complex that binds to FcγRI promoter elements. Furthermore, the tyrosine phosphorylation of STAT1 and the tyrosine kinases JAK1 and JAK2 was enhanced significantly in RGD-adherent monocytes compared with control cells. These results suggest a novel mechanism by which integrin-mediated cell adhesion can modulate the magnitude of cytokine-induced signal transduction pathways, thereby amplifying cellular events leading to monocyte activation and inflammation.

Original languageEnglish (US)
Pages (from-to)2424-2430
Number of pages7
JournalJournal of Immunology
Volume159
Issue number5
StatePublished - Dec 1 1997

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    McCarthy, J. B., Vachhani, B. V., Wahl, S. M., Finbloom, D. S., & Feldman, G. M. (1997). Human monocyte binding to fibronectin enhances IFN-γ-induced early signaling events. Journal of Immunology, 159(5), 2424-2430.