Leukotrienes stimulate phosphatidylcholine secretion in cultured type II pneumocytes.
We previously reported that arachidonic acid stimulates secretion of phosphatidylcholine in cultures of type II pneumocytes and, based on studies with cyclooxygenase and lipoxygenase inhibitors, suggested that this effect was mediated by lipoxygenase products of arachidonic acid metabolism (Gilfillan, A.M. and Rooney, S.A. (1985) Biochim. Biophys. Acta 833, 336-341). We have now examined the effect of leukotrienes on phosphatidylcholine secretion in type II cells as well as the effect of a leukotriene antagonist, FPL55712, on the stimulatory effect of arachidonic acid. Leukotrienes C4, D4 and E4 stimulated phosphatidylcholine secretion and this effect was dependent on concentration in the range 10(-12)-10(-6) M. Leukotriene E4 was the most stimulatory, followed by D4 and C4. Leukotriene B4 had no effect. Incubation of the cells with 10(-7) M leukotriene E4 for 90 min resulted in a 107% increase in the rate of phosphatidylcholine secretion. Incubation with 10(-6) M leukotrienes D4 and C4 for the same period resulted in 81% and 63% stimulation, respectively. The leukotrienes had no effect on cellular phosphatidylcholine synthesis or on lactate dehydrogenase release. The stimulatory effects of leukotrienes E4 and D4 were abolished by FPL55712. Similarly, the stimulatory effect of 6 X 10(-6) M arachidonic acid on phosphatidylcholine secretion was reduced from 74% to 25% by 10(-5) M FPL55712. Thus, the stimulatory effect of arachidonic acid on surfactant phospholipid secretion in type II cells is mediated at least in part by leukotrienes.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007975:Leukotriene B4 / Q000494:pharmacology*; D017999:Leukotriene E4; D008168:Lung / Q000166:cytology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology*; D013997:Time Factors
D001095:Arachidonic Acids; D002867:Chromones; D010713:Phosphatidylcholines; D013189:SRS-A; D007975:Leukotriene B4; D016718:Arachidonic Acid; D017999:Leukotriene E4; C006312:FPL 55712; D007770:L-Lactate Dehydrogenase; D002794:Choline