EFFECTS OF LEUKOTRIENE C-4 AND D-4, HISTAMINE AND BRADYKININ ON CYTOSOLIC CALCIUM CONCENTRATIONS AND ADHESIVENESS OF ENDOTHELIAL-CELLS AND NEUTROPHILS

We compared the effects of leukotrienes B-4, C-4 and D-4 (LTB(4), C-4 and D-4) 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 tra nsients, [Ca2+](i), in vitro. LTB(4), but not LTC(4) or LTD(4) (at 1-1 00 nM), increased HUVEC adhesiveness for PMN, maximally 2.8-fold; in a ddition, PMN adhesion was augmented by LTB(4) (but not by LTC(4) and L TD(4)) to a plastic surface. Rapid, but smaller increments of HUVEC (b ut not of PMN) adhesiveness were induced by histamine and bradykinin ( at 10 mu M). Nonetheless, LTC(4) and LTD(4) (at 100 nM) induced rapid rises of [Ca2+](i) in HUVEC, whereas approximate to 100-fold higher co ncentrations were needed of histamine and bradykinin for similar rises . In PMN LTD(4) (and LTB(4)) induced rapid increases of [Ca2+](i), whe reas no significant effect was seen with LTC(4), histamine or bradykin in. The [Ca2+](i) responses to LTC(4) and LTD(4) were inhibited by the peptidoleukotriene receptor blocker SKF 104,353. Thus, LTB(4) and the peptidoleukotrienes display disparate profiles as inducers of adhesio n and calcium transients in PMN and HUVEC, indicating discrete differe nces in the stimulus response coupling for these closely related leuko trienes.