Comparative actions of biologic and synthetic leukotrienes on isolated human bronchus and rat mast cells

The effects of biologically prepared leukotriene C4 (LTCb) and leukotriene D4 (LTDb), obtained from rat monocytes stimulated with the calcium ionophore A23187, were compared with those of chemically synthetized leukotrienes (LTCs and LTDs) using two in vitro systems. All four leukotriene preparations (10(-10) to 6 X 10(-6) M) showed equal activity upon human bronchi, inducing slow, sustained contractions. LTCb alone (10(-7) to 6.9 X 10(-7) M) elicited histamine release and enhanced compound 48/80-induced release in a dose-dependent manner from rat mast cells. In contrast, LTDb alone was without effect but inhibited release caused by 48/80. FPL 55712 failed to block the LTCb and LTDb effects on the release process. The synthetic leukotrienes neither caused histamine release nor modulated 48/80-induced release from rat mast cells. We conclude that biologic and synthetic leukotrienes exhibit comparable contractile activity on isolated human bronchi but only biologic preparations modulate histamine release by previously unappreciated substances that isolate with the biologic leukotrienes.