This Article Full Text Full Text (PDF) All Versions of this Article: 22/12/1984    most recent 01.ATV.0000043664.48689.7Fv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sajid, M. Articles by Bray, P. F. Search for Related Content PubMed PubMed Citation Articles by Sajid, M. Articles by Bray, P. F. Related Collections Transplantation Other anticoagulants Valvular heart disease Autonomic, reflex, and neurohumoral control of circulation

(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

This article has been cited by other articles:

				K. V. Vijayan and P. F. Bray Molecular Mechanisms of Prothrombotic Risk Due to Genetic Variations in Platelet Genes: Enhanced Outside-In Signaling Through the Pro33 Variant of Integrin {beta}3. Experimental Biology and Medicine, May 1, 2006; 231(5): 505 - 513. [Abstract] [Full Text] [PDF]

				M. U. Naik and U. P. Naik Junctional adhesion molecule-A-induced endothelial cell migration on vitronectin is integrin {alpha}v{beta}3 specific J. Cell Sci., February 1, 2006; 119(3): 490 - 499. [Abstract] [Full Text] [PDF]

				S E Bojesen, S K Kjaer, E V S Hogdall, B L Thomsen, C K Hogdall, J Blaakaer, A Tybjaerg-Hansen, and B G Nordestgaard Increased risk of ovarian cancer in integrin {beta}3 Leu33Pro homozygotes Endocr. Relat. Cancer, December 1, 2005; 12(4): 945 - 952. [Abstract] [Full Text] [PDF]

				K. V. Vijayan, Y. Liu, W. Sun, M. Ito, and P. F. Bray The Pro33 Isoform of Integrin {beta}3 Enhances Outside-in Signaling in Human Platelets by Regulating the Activation of Serine/Threonine Phosphatases J. Biol. Chem., June 10, 2005; 280(23): 21756 - 21762. [Abstract] [Full Text] [PDF]

				J. Mikkelsson, M. Perola, and P. J. Karhunen Genetics of Platelet Glycoprotein Receptors: Risk of Thrombotic Events and Pharmacogenetic Implications Clinical and Applied Thrombosis/Hemostasis, April 1, 2005; 11(2): 113 - 125. [Abstract] [PDF]

				S. E. Bojesen, A. Tybjaerg-Hansen, and B. G. Nordestgaard Integrin {beta}3 Leu33Pro Homozygosity and Risk of Cancer J Natl Cancer Inst, August 6, 2003; 95(15): 1150 - 1157. [Abstract] [Full Text] [PDF]

				K. V. Vijayan, Y. Liu, J.-F. Dong, and P. F. Bray Enhanced Activation of Mitogen-activated Protein Kinase and Myosin Light Chain Kinase by the Pro33 Polymorphism of Integrin beta 3 J. Biol. Chem., January 31, 2003; 278(6): 3860 - 3867. [Abstract] [Full Text] [PDF]