| Autor: |
Laterra J; Department of Neurology, Kennedy Krieger Research Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205., Indurti RR, Goldstein GW |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of cellular physiology [J Cell Physiol] 1994 Feb; Vol. 158 (2), pp. 317-24. |
| DOI: |
10.1002/jcp.1041580214 |
| Abstrakt: |
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). Endothelia-derived uPA activity decreased sevenfold within glial-endothelial cocultures when capillary-like structures were formed. Incubation of cocultures with concentrations of phorbol 12-myristate 13-acetate (0.1 and 1.0 nM) that induced endothelial uPA activity (45-210%) inhibited endothelial differentiation (25-70%). 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/plasmin 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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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