IN-VIVO EVIDENCE OF THE CRITICAL ROLE OF CADHERIN-5 IN MURINE VASCULAR INTEGRITY

Vascular endothelial cell-cell adhesion is crucial for the regulation of vascular functions and is associated with many circulatory disorder s. We isolated a rat monoclonal antibody (VECD1) recognizing the mouse vascular endothelial cell adhesion molecule and found that it inhibit ed vascular endothelial cell-cell association. We sequenced a full-len gth cDNA of the antigen that was identical to mouse cadherin-5. L-cell s transfected with its cDNA acquired cell-cell adhesiveness, and these transfectants reacted with VECD I at cell-cell contact areas. We stud ied the role of mouse cadherin-5 in vascular functions. The addition o f VECD1 antibody to a cultured vascular endothelial cell line (F-2) ca used the detachment of each cell. Although normal F-2 cells formed tub ular structures on Matrigel, VECD1 disturbed the tubulogenesis. VECD1 also increased the permeability through the F-2 cell layer. To clarify the in vivo function of mouse cadherin-5, we intraperitoneally inject ed the hybridomas producing VECD1. into adult mice. Severe venous stas is and subcutaneous hemorrhage were induced within several days after the injection, resulting in the early death of the animals. These find ing are evidence of an essential role of cadherin-5 in the regulation of vascular endothelial cell-cell adhesion in vivo.