Differentiation of endothelial barrier function during normal angiogenesisrequires homotypic VE-cadherin adhesion

Endothelial cells express two principal cadherins: VE-cadherin and N-cadher in. We established previously that only VE-cadherin expression was increase d during differentiation of barrier function by angiogenic endothelium of t he chick chorioallantoic membrane (CAM). Presently anti-VE-cadherin mAb, ap plied to the CAM at day 4.5 of gestation, served to inhibit the abrupt redu ction of macromolecular extravasation that occurs normally at day 5.0. Neit her anti-N-cadherin nor nonimmune IgG, on the other hand, prevented this te mporal decrease of endothelial permeability. Despite the differential perme ability responses, morphometric evaluations defined a reduction of mean par acellular cleft width after the application of either anti-VE-cadherin or a nti-N-cadherin. Hence, alteration of molecular sieving characteristics with in the junctional clefts, rather than modification of cleft dimensions; lik ely served as the principal modulator of macromolecular extravasation after inhibition of homotypic VE-cadherin adhesion. These results provide suppor t to the concept that VE-cadherin contributes to the normal differentiation of endothelial barrier function during CAM angiogenesis in vivo. (C) 2000 Harcourt Publishers Ltd.