Formula omitted] integrin complex mediates the differentiation of human endothelial cells into capillary-like structures in vitro

Abstract

We have investigated different β-1 integrins ( CDw49 CD29 ) on human umbilical vein endothelial cells (HUVEC) with regard to their roles in modifying the morphological structure of these cells on/in matrigel. The inhibition of matrigel-induced capillary formation by antibodies against subunits of β-1 integrins was examined quantitatively using a digital analyzer. Antibodies to CDw49b and CD29 (common beta chain) caused a marked inhibition of capillary formation (up to 70%) in a dose-dependent manner, whereas antibodies to CDw49d, CDw49e and CDw49f were less inhibitory. We also examined the appearance of HUVEC cultured in matrigel. HUVEC suspended in matrigel for 24 h formed extended cell processes which connected, resulting in the formation of a capillary network. In contrast, fibroblasts cultured in matrigel showed only bipolar extensions without cell-cell contact. After 48 h in culture in matrigel, some HUVEC showed the capillary-unit of a lumen encircled by EC which may mimic the basic putative unit in the formation of capillaries. However, HUVEC pretreated with antibodies to CDw49b and CD29 failed to form significant processes and a hollow lumen. These phenomena may illustrate the importance of endothelial cell-basement membrane matrix interaction (through integrins, especially CDw49 b CD29 complex) occurring during differentiation of endothelial cells in angiogenesis.