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.
Lee
R T
RT
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Berditchevski
F
F
Cheng
G C
GC
Hemler
M E
ME
D002448:Cell Adhesion; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D005782:Gels; D006801:Humans; D016023:Integrins / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D011233:Precipitin Tests
D005782:Gels; D016023:Integrins; D003094:Collagen