COSTIMULATION OF FIBRONECTIN RECEPTOR PROMOTES FC-GAMMA-R-MEDIATED RESCUE OF IL-3-DEPENDENT BONE-MARROW-DERIVED CELLS FROM APOPTOSIS

The IL-3-dependent murine bone marrow-derived cell line FDC-P2/185-4 ( 185-4) undergoes apoptosis when IL-3 is withdrawn from the culture med ium, However, a high concentration of aggregated mouse IgG prevents ap optosis of 185-4 cells by an autocrine mechanism, producing IL-3, An a nalysis 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 concent ration of mouse IgG cannot prevent the apoptosis of 185-4 cells, but i n the presence of fibronectin (FN), cell survival is prolonged, It is generally accepted that the interaction of cells with FN is mediated b y 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 exp ress these integrins on their surface, Furthermore, these effects of F N are blocked specifically by RGD peptide or anti-VLA-4 mAb, These fin dings indicated that FN induces the costimulatory signal through integ rin receptor and enhances the proliferative effect through Fc gamma RI II by a low concentration of IgG. The findings presented here suggeste d that the engagement of FN-integrin receptors on 185-4 cells increase s the sensitivity of the cells for cellular activation by IgG, Since i nflammatory cells in the microenvironment are surrounded by extracellu lar matrix proteins, it is possible that adhesion molecules play impor tant roles in inflammatory states such as autoimmune diseases caused b y increased levels of IgG.