Leukotriene B-4-activated human endothelial cells promote transendothelial neutrophil migration

We explored the effect of leukotriene B-4 (LTB4) on endothelial cells in LTB4-induced transendothelial migration (TEM) of neutrophils as an in vitro model of neutrophil extravasation, Chemotactic response of human neutrophils to LTB4 was significantly lower than that in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP), whereas the extent of TEM in response to LTB4 was significantly higher than that to fMLP. The study on random migration induced by LTB4 and fMLP also showed similar results, which indicated that LTB4 might affect the human umbilical cord vein endothelial cell (HUVEC) barrier, Neutrophil TEM was induced by pretreatment of HUVEC monolayer with LTB4 but not with fMLP, Treatment of endothelial cells by ONO-4057, a LTB4 receptor antagonist, abolished the effect of LTB4 almost completely whereas neutrophils treated with ONO-4057 could transmigrate through HUVEC treated with LTB4. These findings indicated that LTB4 could induce neutrophil TEM by acting on HUVEC.