Regulation of in vitro glia-induced microvessel morphogenesis by urokinase

✍ Scribed by John Laterra; Ravi R. Indurti; Gary W. Goldstein

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 893 KB
• Volume: 158
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041580214

✦ Synopsis

Plasminogen activators (PAS) regulate a variety of processes involved in tissue morphogenesis and differentiation. We used a coculture system in which microvascular endothelial cells are induced by glial cells to form capillary-like structures in order to examine the role of urokinase-type PA (uPA) during microvessel morphogenesis within the central nervous system (CNS). Endotheliaderived u PA activity decreased sevenfold with in gl ial-endothel ial cocu I tures when capillary-like structures were formed. Incubation of cocultures with concentrations of phorbol 12-myristate 13-acetate (0.1 and 1 .O nM) that induced endothelial uPA activity (45-21 0%) inhibited endothelial differentiation (25-70Y0). Furthermore, incubation of cocultures with proteolytically active low molecular weight uPA (5-500 IU/ml) inhibited endothelial differentiation (37-75%), whereas the amino terminal cell-binding fragment of uPA had minimal effect. Inhibition of plasminogen activation in cocultures with the serine protease/ plasrnin inhibitors aprotinin and soybean trypsin inhibitor increased glia-induced capillary-like structure formation (96-98%). These findings establish a paracrine/ autocrine function for urokinase and its inhibitors in regulating endothelial responses to perivascular glia and provide insight into mechanisms of microvascular reactions to CNS pathology.