The Journal of Immunology, Vol 156, Issue 5 1832-1840, Copyright © 1996 by American Association of Immunologists

ARTICLES

Costimulation of fibronectin receptor promotes Fc gamma R-mediated rescue of IL-3-dependent bone marrow-derived cells from apoptosis

H Yoshikawa, T Sakihama, Y Nakajima and K Tasaka
Department of Parasitology and Immunology, Yamanashi Medical University, Japan.

The IL-3-dependent murine bone marrow-derived cell line FDC-P2/185-4 (185-4) undergoes apoptosis when IL-3 is withdrawn from the culture medium. However, a high concentration of aggregated mouse IgG prevents apoptosis of 185-4 cells by an autocrine mechanism, producing IL-3. An analysis of flow cytometry revealed that 185-4 cells expressed Fc gamma RIII on their surface and that these effects of IgG are inhibited by anti-Fc gamma RIII mAb. These results indicated that the effect of IgG is mediated by low affinity Fc gamma RIII. In contrast, a low concentration of mouse IgG cannot prevent the apoptosis of 185-4 cells, but in the presence of fibronectin (FN), cell survival is prolonged. It is generally accepted that the interaction of cells with FN is mediated by several integrins such as alpha 5 beta 1 (VLA-5) or alpha 4 beta 1 (VLA-4), and analysis of flow cytometry showed that 185-4 cells express these integrins on their surface. Furthermore, these effects of FN are blocked specifically by RGD peptide or anti-VLA-4 mAb. These findings indicated that FN induces the costimulatory signal through integrin receptor and enhances the proliferative effect through Fc gamma RIII by a low concentration of IgG. The findings presented here suggested that the engagement of FN-integrin receptors on 185-4 cells increases the sensitivity of the cells for cellular activation of IgG. Since inflammatory cells in the microenvironment are surrounded by extracellular matrix proteins, it is possible that adhesion molecules play important roles in inflammatory states such as autoimmune diseases caused by increased levels of IgG.

This article has been cited by other articles:

				L. T. Tomte, Y. Annatshah, N. K. Schluter, N. Miosge, R. Herken, and F. Quondamatteo Hematopoietic Cells Are a Source of Nidogen-1 and Nidogen-2 during Mouse Liver Development. J. Histochem. Cytochem., May 1, 2006; 54(5): 593 - 604. [Abstract] [Full Text] [PDF]

				H. Yoshikawa, Y. Nakajima, and K. Tasaka Enhanced Expression of Fas-Associated Death Domain-Like IL-1-Converting Enzyme (FLICE)-Inhibitory Protein Induces Resistance to Fas-Mediated Apoptosis in Activated Mast Cells J. Immunol., December 1, 2000; 165(11): 6262 - 6269. [Abstract] [Full Text] [PDF]

				Y. L. Kapila, S. Wang, and P. W. Johnson Mutations in the Heparin Binding Domain of Fibronectin in Cooperation with the V Region Induce Decreases in pp125FAK Levels Plus Proteoglycan-mediated Apoptosis via Caspases J. Biol. Chem., October 22, 1999; 274(43): 30906 - 30913. [Abstract] [Full Text] [PDF]

				H. Yoshikawa, Y. Nakajima, and K. Tasaka Glucocorticoid Suppresses Autocrine Survival of Mast Cells by Inhibiting IL-4 Production and ICAM-1 Expression J. Immunol., May 15, 1999; 162(10): 6162 - 6170. [Abstract] [Full Text] [PDF]

				L. L. Chen, A. Whitty, R. R. Lobb, S. P. Adams, and R. B. Pepinsky Multiple Activation States of Integrin alpha 4beta 1 Detected through Their Different Affinities for a Small Molecule Ligand J. Biol. Chem., May 7, 1999; 274(19): 13167 - 13175. [Abstract] [Full Text] [PDF]

				H. Yoshikawa, T. Sakihama, Y. Nakajima, and K. Tasaka Fcgamma RIII-Mediated Regulation of Hematopoiesis in Murine Bone Marrow Cells by Interleukin-3 and CD95 (Fas/Apo-1) Blood, September 1, 1997; 90(5): 1911 - 1919. [Abstract] [Full Text] [PDF]

				L. L. Chen, A. Whitty, D. Scott, W.-C. Lee, M. Cornebise, S. P. Adams, R. C. Petter, R. R. Lobb, and R. B. Pepinsky Evidence That Ligand and Metal Ion Binding to Integrin alpha 4beta 1 Are Regulated through a Coupled Equilibrium J. Biol. Chem., September 21, 2001; 276(39): 36520 - 36529. [Abstract] [Full Text] [PDF]