Priming effects of leukotriene B4 on endothelial cell injury induced by tpa-activated leukocytes

Among arachidonic acid metabolites, leukotriene B₄ (LTB₄) plays an important role in inflammation, such as in the activation, adhesion, chemotaxis, and invasion of leukocytes. In this paper, we examined the effect of LTB₄ on endothelial cell injury induced by polymorphonuclear leukocytes (PMNLs).⁵¹Crrelease, a marker of cellular injury, was elicited from prelabeled endothelial cells when the cells were cocultured with PMNLs activated by phorbol ester (TPA, 12-0-tetradecanoyl-phorbol-13-acetate). Under this condition, pretreatment of PMNLs with LTB₄ enhanced their injury in a dose-dependent manner (0.2–2 M). However, LTB₄ alone at any dose could not induce any cellular injury. We also determined the amount of active oxygen species produced by PMNLs in response to TPA. The intensity of luminoldependent chemiluminescence, a marker of active oxygen production, in PMNLs was also increased by pretreatment with 1 M LTB₄. These data suggest that LTB₄ enhances endothelial cell injury by the priming effect on active oxygen production in activated PMNLs.