BRAIN ENDOTHELIUM LACK ONE OF 2 PATHWAYS OF P-SELECTIN-MEDIATED NEUTROPHIL ADHESION

P-selectin, an endothelial leukocyte adhesion receptor, is rapidly tra nslocated to the cell surface upon release from storage granules calle d Weibel-Palade bodies and is also transcriptionally upregulated upon cytokine stimulation of endothelial cells (ECs). These two pathways of surface expression are coincident with the rapid and cytokine-inducib le pathway of neutrophil adhesion to ECs. Constitutive P-selectin expr ession is largely absent in cultured murine brain microvascular EC (BM EC) monolayers, but interleukin-1 beta and tumor necrosis factor-alpha stimulation for 4 hours leads to dramatic P-selectin upregulation. Th e functional relevance of differential P-selectin expression in these cells was examined by studying BMECs derived from wild-type mice and P -selectin-deficient mice. We show that P-selectin deficiency does not affect Weibel-Palade body formation or their release in response to sh ort-acting agonists. However, in the absence of P-selectin, the brain endothelium is unable to support neutrophil adhesion after stimulation with these agonists, which may contribute to the immune privilege sta tus of the brain. We show that P-selectin does play a major role in su pporting neutrophil adhesion in the cytokine-induced pathway in BMECs in the context of other cytokine-inducible endothelial-leukocyte adhes ion receptors, E-selectin, ICAM-1, and VCAM-1. (C) 1996 by The America n Society of Hematology.