C5A-INDUCED EXPRESSION OF P-SELECTIN IN ENDOTHELIAL-CELLS

Human umbilical vein endothelial cells have recently been shown to res pond to C5a with increases in intracellular Ca2+, production of D-myo- inositol 1,4,5-triphosphate and superoxide anion generation. In the cu rrent studies, C5a has been found to cause in a time- and dose-depende nt manner rapid expression of endothelial P-selectin, secretion of von Willebrand factor, and adhesiveness for human neutrophils. The effect s of C5a in P-selectin expression and adhesiveness of neutrophils were similar to the effects of histamine and thrombin on endothelial cells . The adhesiveness of C5a-stimulated endothelium for neutrophils was b locked by anti-P-selectin, but not by antibodies to intercellular adhe sion molecule 1, E-selectin, or CD18. A cell-based ELISA technique has confirmed upregulation of P-selectin in endothelial cells exposed to C5a. Binding of C5a to endothelial cells has been demonstrated, with m olecules bound being similar to 10% of those binding to neutrophils. B y a reverse transcriptase-PCR technique, endothelial cells have been s hown to contain mRNA for the C5a receptor. These data suggest that C5a may be an important inflammatory mediator for the early adhesive inte ractions between neutrophils and endothelial cells in the acute inflam matory response.