Effects of leukotriene C4 and D4, histamine and bradykinin on cytosolic calcium concentrations and adhesiveness of endothelial cells and neutrophils

Abstract

We compared the effects of leukotrienes B4, C4 and D4 (LTB4, C4 and D4) in vitro, as well as of histamine and bradykinin, on adhesive interactions between cultured umbilical vein endothelial cells (HUVEC) and polymorphonuclear neutrophils (PMN) and on cytosolic calcium transients, [Ca2+](i), in vitro. LTB4, but not LTC4 or LTD4 (at 1-100 nM), increased HUVEC adhesiveness for PMN, maximally 2.8-fold; in addition, PMN adhesion was augmented by LTB4 (but not by LTC4 and LTD4) to a plastic surface. Rapid, but smaller increments of HUVEC (but not of PMN) adhesiveness were induced by histamine and bradykinin (at 10 μM). Nonetheless, LTC4 and LTD4 (at 100 nM) induced rapid rises of [Ca2+](i) in HUVEC, whereas ~ 100-fold higher concentrations were needed of histamine and bradykinin for similar rises. In PMN LTD4 (and LTB4) induced rapid increases of [Ca2+](i), whereas no significant effect was seen with LTC4, histamine or bradykinin. The [Ca2+](i) responses to LTC4 and LTD4 were inhibited by the peptidoleukotriene receptor blocker SKF 104,353. Thus, LTB4 and the peptidoleukotrienes display disparate profiles as inducers of adhesion and calcium transients in PMN and HUVEC, indicating discrete differences in the stimulus response coupling for these closely related leukotrienes.