Lee R T, Berditchevski F, Cheng G C, Hemler M E
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Circ Res. 1995 Feb;76(2):209-14. doi: 10.1161/01.res.76.2.209.
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.
血管平滑肌细胞在调节血管细胞外基质方面发挥着重要作用。由于整合素介导多种细胞与基质的相互作用，因此研究了整合素在培养的人血管平滑肌细胞对胶原蛋白的重组过程中的作用。免疫沉淀实验表明，人血管平滑肌细胞表达多种β1整合素。单克隆抗体A2-IIE10（一种抗α2阻断抗体）可使平滑肌细胞与胶原蛋白的黏附减少31%。抗α1阻断抗体1B3.1可使黏附减少40%，而抗α3阻断抗体对黏附没有影响。当同时使用1B3.1和A2-IIE10时，黏附减少了79%，这表明活性α1和α2整合素协同介导黏附。抗β1阻断抗体Mab13消除了平滑肌细胞介导的凝胶收缩，α2阻断抗体A2-IIE10具有剂量依赖性的部分抑制作用（37%）。相比之下，抗α1和抗α3阻断抗体没有作用。当抗α1（1B3.）和抗α2（A2-IIE10）单克隆抗体联合使用时，未观察到对凝胶收缩抑制的协同作用。令人惊讶的是，一种以刺激细胞黏附而闻名的抗β1抗体（TS2/16）可使胶原蛋白凝胶收缩受到46%的抑制。因此，虽然α1β1和α2β1整合素都参与血管平滑肌细胞与胶原蛋白的黏附，但只有α2β1整合素介导胶原蛋白的重组。此外，胶原蛋白的重组似乎是一个动态过程，过度增强黏附会对其产生不利影响。
