Glycoprotein Ibα Can Mediate Endothelial Cell Migration on von Willebrand Factor-Containing Substrata

Abstract

We have previously shown that, in addition to the vitronectin receptor (VNR, αvβ3), the GP Ib complex can participate in endothelial cell (EC) attachment to von Willebrand Factor (vWF) (D. A. Beacham, M. S. Cruz, and R. I. Handin, 1995, Thromb. Haemostas. 73, 309–317; D. A. Beacham, L.-P. Tran, and S. S. Shapiro, 1997, Blood 89, 4071–4077). In this study we have investigated the functional roles of these vWF receptors in the migration of untreated and TNFα-treated EC on vWF, a mixture of vWF and type I collagen, and on vitronectin (VN). In agreement with previous studies (D. I. Leavesley, M. A. Schwartz, M. Rosenfeld, and D. A. Cheresh, 1993, J. Cell Biol. 121, 163–170), the migration of untreated and TNFα-treated EC on VN was dependent entirely on the VNR. Migration of untreated EC on vWF was inhibited 10–15% by recombinant vWF-A1, the GP Ibα-binding domain on vWF which abrogates the platelet GP Ibα–vWF interaction. In contrast, migration of TNFα-treated EC on vWF was inhibited 50–60% by vWF-A1 or the anti-GP Ibα mAb AS-7 but only 20% by the anti-VNR mAb LM609. On a mixed vWF–collagen substratum, vWF-A1 inhibited untreated EC migration by 45%, and TNFα-treated EC migration by 75%. The possible role of EC proliferation was eliminated, since hydroxyurea completely inhibited EC proliferation without reducing migration significantly. The anti-GP Ibα mAb Ib1 inhibited EC migration by 50%, but reduced proliferation by only 15%. Taken together, our data demonstrate that EC migration on vWF-containing substrata involves the GP Ib complex as well as the VNR and raises the possibility that the VNR and GP Ib act cooperatively in supporting EC migration.