Leukotriene B4-activated human endothelial cells promote transendothelial neutrophil migration

Abstract

We explored the effect of leukotriene B₄ (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. J. Leukoc. Biol. 62: 203–209; 1997.