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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:1984.)
© 2002 American Heart Association, Inc.

Vascular Biology

Pl^A Polymorphism of Integrin ß₃ Differentially Modulates Cellular Migration on Extracellular Matrix Proteins

Mansoor Sajid; K. Vinod Vijayan; Shiloe Souza; Paul F. Bray

From the Department of Medicine, Baylor College of Medicine, Houston, Tex.

Correspondence to Paul F. Bray, MD, Thrombosis Research Section, Baylor College of Medicine, One Baylor Plaza, BCM 286, N1319, Houston, TX 77030. E-mail pbray{at}bcm.tmc.edu

Objective— Cell migration is central to multiple physiological and pathologic processes and involves interactions between integrins on the cell surface and the extracellular matrix. The Leu33Pro (Pl^A) polymorphism of integrin ß₃ has been reported to be associated with a greater rate of restenosis after angioplasty, a process involving endothelial and smooth muscle cell migration. We have addressed the possibility that the Leu33Pro polymorphism could modify the migratory behavior of Chinese hamster ovary (CHO) cells expressing the ß₃-containing integrin complexes.

Methods and Results— Haptotactic migratory responses of CHO _IIbß₃ cells to fibronectin and vitronectin were not statistically different between the Leu33 and Pro33 cells. However, CHO cells with the Pro33 (Pl^A2) polymorphism had an enhanced haptotactic migratory response to fibrinogen and von Willebrand Factor. This enhanced migration (1) could be blocked by the _IIbß₃-complex–specific neutralizing mAb 10E5, by 7E3, a neutralizing mAb specific for the ß₃ integrin, and by the _IIbß₃-blocking peptide Integrilin; (2) was not observed with a CHO cell line expressing an activating ß₃ Cys435 to Ala mutation; and (3) was attributable to increased activity of mitogen-activated protein kinase and cyclooxygenase. CHO cell lines expressing the Pro33 isoform of _vß₃ had an enhanced haptotactic migratory response to vitronectin and osteopontin but not fibrinogen.

Conclusions— The Leu33Pro polymorphism alters the migratory behavior of cells on extracellular matrix substrates, and the subunit influences the substrate specificity of this genetic effect.

Key Words: ß₃ integrin • Pl^A polymorphism • cell migration

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