Prostaglandin E is required for the augmentation of procoagulant activity of LPS-stimulated rabbit alveolar macrophages.
We demonstrated previously that rabbit alveolar macrophages stimulated in vitro by bacterial lipopolysaccharide (LPS) have markedly enhanced procoagulant activity (PCA), caused by increased production of a cell-associated tissue thromboplastin. The present study examined the role of arachidonic acid metabolites in modulating the expression of this PCA. Alveolar macrophages lavaged from normal rabbits were incubated in vitro with LPS, indomethacin, and purified prostaglandins, and the resultant PCA was measured. LPS stimulated a significant increase in macrophage PCA relative to unstimulated controls (p less than 0.01). Indomethacin suppressed the ability of LPS to stimulate PCA in a dose-related fashion. The addition of PGE2 or PGE1 reversed the suppressive action of indomethacin (p less than 0.01), whereas PGF2 alpha, PGD2, TXB2, and 6-keto PGF1 alpha had no such effect. PGE2 did not affect PCA unless the macrophages were also stimulated with LPS. A significant correlation (rs = 0.72, p less than 0.01) existed between the level of LPS-stimulated macrophage PCA and the corresponding amount of immunoreactive PGE2 released into the culture medium. The results of this study demonstrate that PGE is required for the LPS-mediated enhancement of rabbit alveolar macrophage-associated tissue thromboplastin and that PGE can stimulate the expression of PCA by appropriately conditioned cells.
D000818:Animals; D001667:Binding, Competitive; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D015232:Dinoprostone; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology; D011817:Rabbits
D008070:Lipopolysaccharides; D011458:Prostaglandins E; D015232:Dinoprostone; D007213:Indomethacin