INTEGRIN-MEDIATED COLLAGEN MATRIX REORGANIZATION BY CULTURED HUMAN VASCULAR SMOOTH-MUSCLE CELLS

Vascular smooth muscle cells perform the important function of modulation of vascular extracellular matrix. Because integrins mediate many cell-matrix interactions, the role of integrins in reorganization of collagen by cultured human vascular smooth muscle cells was studied. Immunoprecipitation demonstrated that human vascular smooth muscle cells express multiple beta(1) integrins. Monoclonal antibody A2-IIE10 (a blocking anti-alpha(2) antibody) inhibited adhesion of smooth muscle cells to collagen by 31%. The blocking anti-alpha(1) antibody 1B3.1 inhibited adhesion by 40%, whereas a blocking anti-alpha(3) antibody had no effect on adhesion. When 1B3.1 and A2-IIE10 were both used, a 79% reduction in adhesion was observed, indicating that active alpha(1) and alpha(2) integrins cooperatively mediate adhesion. The blocking anti-beta(1) antibody Mab13 abolished smooth muscle cell-mediated gel contraction, and the alpha(2)-blocking antibody A2-IIE10 had a dose-dependent partial inhibitory effect (37%). In contrast, blocking antibodies to alpha(1) and alpha(3) had no effect. When anti-alpha(1) (1B3.1) and anti-alpha(2) (A2-IIE10) monoclonal antibodies were combined, no synergistic effect on inhibition of gel contraction was observed. Surprisingly, collagen gel contraction was inhibited by 46% by an anti-beta(1) antibody (TS2/16) known for its stimulatory effect on cell adhesion. Thus, whereas alpha(1) beta(1) and alpha(2) beta(1) integrins both participate in adhesion of vascular smooth muscle cells to collagen, only alpha(2) beta(1) integrins mediate collagen reorganization. In addition, collagen reorganization appears to be a dynamic process, adversely affected by excessive adhesion strengthening.