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First published online 5 August 2003
doi: 10.1242/jcs.00681

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Endothelial expression of the 6ß4 integrin is negatively regulated during angiogenesis

¹ Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA
² The Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA
³ The Institute for Vascular Health and Disease, Albany Medical College, Albany, NY 12208, USA
⁴ The Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA

^* Author for correspondence (e-mail: laflams{at}mail.amc.edu

Accepted 23 May 2003

Development and homeostasis of the vascular system requires integrin-facilitated cellular adhesion, migration, proliferation and survival. A specific role for the 6ß4 integrin in the vasculature, however, has not been identified. Using immunohistochemistry, we observed 6ß4 expression on the dermal microvasculature of human foreskin. Analysis of individual cells isolated from trypsin-disrupted foreskin tissue indicated that 6ß4 was expressed by a subset of epithelial and endothelial cells, and not by smooth muscle cells. Expression of 6ß4 was also analyzed during new vessel growth using explants of human saphenous vein cultured in fibrinogen gels. The results indicate that 6ß4 is not expressed by outgrowing endothelial cells, and is downregulated by the original 6ß4-positive endothelial cells of the explant. To determine whether 6ß4 is expressed during angiogenesis in vivo, the expression of the ß4 subunit was analyzed during the development of the mouse mystacial (whisker) pad. Immunohistochemical staining of the whisker pad indicates that ß4 is expressed by the adult vasculature. To identify when and where ß4 is turned on in the vasculature, we examined the whisker pads from the developing embryo (E19.5 pc), and from postnatal days zero (P0), three (P3) and seven (P7) pups. The expression of 6ß4 was found to be turned on spatially and temporally from caudal to rostral regions and from the deep to superficial vasculature, correlating with the maturation of the whisker pad and its corresponding vasculature. Together, these findings suggest a potential role for 6ß4 as a negative component of the angiogenic switch, whereas expression of 6ß4 on the adult vasculature may indicate regions requiring additional adhesive mechanisms.

Key words: Endothelial cells, Integrins, 6ß4, Angiogenesis, Development, Explant cultures, Schwann cells

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