POLARIZED EXPRESSION AND BASIC FIBROBLAST GROWTH FACTOR-INDUCED DOWN-REGULATION OF THE ALPHA-6-BETA-4 INTEGRIN COMPLEX ON HUMAN MICROVASCULAR ENDOTHELIAL-CELLS

Endothelial cells rest on a basement membrane that anchors them to the vessel wall. The alpha 6 beta 4 integrin complex has been described o n epithelial cells, frequently localizes to basement-membrane structur es, and appears to play a role in binding epithelial cells to laminin. We have determined that human microvascular endothelial cells express the beta 4 integrin chain in vivo and that it preferentially localize s to the endothelial basement membrane. Human microvascular endothelia l cells and human umbilical vein endothelial cells also express cell-s urface beta 4 in vitro. In addition, the expression of beta 4 appears to be polarized to the undersurface of endothelial cell monolayers in vitro, mimicking its in vivo localization. Stimulation of microvascula r endothelial cells with basic fibroblast growth factor or phorbol 12- myristate 13-acetate, agents previously shown to induce endothelial ce ll migration in vitro, resulted in a marked decrease in cell-surface e xpression of the beta 4 integrin chain, associated with a decrease in beta 4 mRNA. These data demonstrate that human endothelial cells expre ss the beta 4 integrin chain in vivo and in vitro, the expression is r egulated on microvascular endothelial cells by factors important in wo und healing and vascular regeneration.