ANTI-FX1A ANTIBODY RECOGNIZES A BETA-1-INTEGRIN ON GLOMERULAR EPITHELIAL-CELLS AND INHIBITS ADHESION AND GROWTH

Cell-matrix interactions play an important role in regulating cell growth and metabolic activity and potentially in maintaining the integrity of the glomerular filtration barrier. The effect of anti-Fx1A antibody (Ab), the pathogenetic Ab of passive Heymann nephritis, on the interaction of cultured rat glomerular visceral epithelial cells (GEC) with matrix components was examined in an effort to determine whether it affects cell adhesion. Affinity chromatography demonstrated that anti-Fx1A recognizes an alpha(3)beta(1)-integrin-type matrix receptor on GEC. Anti-Fx1A inhibited the adhesion of GEC to several substrates (collagen IV congruent-to collagen I < laminin congruent-to fibronectin) in a dose-dependent manner and produced reversible cell detachment and "rounding up" when added to adherent cells. Maximal inhibition of adhesion was similar with anti-Fx1A and anti-beta(1), and competition studies showed no additive effects between anti-Fx1A and anti-beta(1) in inhibiting adhesion, suggesting that the effect of anti-Fx1A on GEC adhesion is attributable to its anti-beta(1) activity. Anti-Fx1A Ab also inhibited the growth of GEC in culture without evidence of cytotoxicity, and cells resumed normal growth on removal of Ab. These studies suggest that anti-Fx1A Ab can bind to matrix receptors on GEC, resulting in inhibition of cell attachment and growth, as well as producing detachment of cells that are already adherent. Interference with GEC-glomerular basement membrane interactions in vivo might have significant effects on glomerular permeability to proteins.