BASIC FIBROBLAST GROWTH-FACTOR MODULATES INTEGRIN EXPRESSION IN MICROVASCULAR ENDOTHELIAL-CELLS

During angiogenesis capillary endothelial cells undergo a coordinated set of modifications in their interactions with extracellular matrix c omponents. In this study we have investigated the effect of the protot ypical angiogenic factor basic fibroblast growth factor (bFGF) on the expression and function of several integrins in microvascular endothel ial cells. Immunoprecipitation experiments with antibodies to individu al subunits indicated that microvascular cells express at their surfac e several integrins. These include the alpha 1 beta 1, alpha 2 beta 1, and alpha 3 beta 1 laminin/collagen receptors; the alpha 6 beta 1 lam inin receptor; the alpha 5 beta 1 and alpha v beta 1 fibronectin recep tors; the alpha 6 beta 4 basement membrane receptor; and the alpha v b eta 3 and alpha v beta 5 vitronectin receptors. Treatment with bFGF ca used a significant increase in the surface expression of the alpha 2 b eta 1, alpha 3 beta 1, alpha 5 beta 1, alpha 6 beta 1, alpha 6 beta 4, and alpha v beta 5 integrins. In contrast, the level of expression of the alpha 1 beta 1 and alpha v beta 3 integrins was decreased in bFGF -treated cells. Immunoprecipitation of metabolically labeled cells ind icated that bFGF increases the biosynthesis of the alpha 3, alpha 5, a lpha 6, beta 4, and beta 5 subunits and decreases the production of th e alpha v and beta 3 subunits. These results suggest that bFGF modulat es integrin expression by altering the biosynthesis of individual alph a or beta subunits. In accordance with the upregulation of several int egrins observed in bFGF-treated cells, these cells adhered better to f ibronectin, laminin, vitronectin, and type I collagen than did untreat ed cells. The largest differences in beta 1 integrin expression occurr ed similar to 72 h after exposure to bFGF, at a time when the expressi on of the endothelial cell-to-cell adhesion molecule endoCAM was also significantly upregulated. In contrast, a shorter exposure to bFGF (24 -48 h) was required for the maximal induction of plasminogen activator production in the same cells. Taken together, these results show that bFGF causes significant changes in the level of expression and functi on of several integrins in microvascular endothelial cells.