Analysis of roles of platelet activating factor in neutrophil transendothelial migration.
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概要
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In an air pouch type allergic inflammation model in rats, PAF antagonists inhibit neutrophil migration into the pouch fluid although levels of PAF in the pouch fluid are less than the detectable amount. To clarify roles of PAF in neutrophil migration, effects of PAF antagonists (CV-6209, L-652, 731, Y-24180) on transendothelial migration of neutrophils were examined <I>in vitro</I>. Histamine and thrombin stimulated LTB4-induced transmigration of neutrophils through the confluent monolayer of human umbilical vein endothelial cells (HUVEC) . Treatment with PAF antagonists selectively inhibited the histamine- and thrombin-induced transendothelial migration, suggesting that PAF plays some significant roles in endothelial cell recognition by neutrophils.<BR>Treatment of HUVEC with TNF-α or IL-1/β induced neutrophil adherence to HUVEC monolayer and expression of adhesion molecules, such as ICAM-1, ELAM-1 or GMP-140. However, PAF antagonists showed no effect on the cytokine-induced neutrophil adherence to HUVEC nor the expression of these adhesion molecules. Furthermore, histamine- and thrombin-induced neutrophil adherence to HUVEC was inhibited by PAF antagonists without altering the expression of these adhesion molecules.<BR>Transendothelial migration of neutrophils was not inhibited by antibodies to GMP-140 and ELAM-1, but was completely inhibited by an antibody to LFA-1/β. An antibody to ICAM-1 partially inhibited the transendothelial migration of neutrophils.<BR>These results suggest that PAF produced by HUVEC plays important roles in signaling for neutrophil adherence to endothelial cells without affecting the expression of these adhesion molecules.
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