Platelet-activating factor induces the production of leukotrienes by human monocytes.
The aim of this study was to evaluate the role of platelet-activating factor (PAF) as a stimulator of leukotriene production by human monocytes. The production of leukotrienes was time- and concentration-dependent. Release of leukotrienes was half-maximal after 2 min and reached a maximum after 10 min. At a concentration of 10(-8) M, PAF induced the production of 0.14 +/- 0.01 ng LTB4/10(6) cells (mean +/- S.E., n = 8). At concentrations of 10(-6) M, PAF induced the production of 1.0 +/- 0.04 ng LTB4 and 0.22 +/- 0.03 ng peptidoleukotrienes (mean +/- S.E., n = 16). There was no metabolism of LTB4 as judged from stability of [3H]LTB4 added to the incubations. LTC4 was slowly metabolized by human monocytes to LTD4 and LTE4. The two specific PAF-receptor antagonists BN 52021 and WEB 2086 in concentrations of 10(-4) and 10(-6) M, respectively, inhibited the PAF (10(-6) M) stimulated LTB4 production completely. In this study, we demonstrate that nanomolar concentrations of PAF can stimulate the production of LTB4 and peptidoleukotrienes in human monocytes by a receptor-mediated mechanism.
Fauler
J
J
Department of Clinical Pharmacology, Hannover Medical School, F.R.G.
Sielhorst
G
G
Frölich
J C
JC
D001381:Azepines / Q000494:pharmacology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes; D046934:Ginkgolides; D006801:Humans; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D015289:Leukotrienes / Q000096:biosynthesis / Q000097:blood* / Q000302:isolation & purification; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles
D001381:Azepines; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D015289:Leukotrienes; D010936:Plant Extracts; D010972:Platelet Activating Factor; D014227:Triazines; D014230:Triazoles; C052518:WEB 2086; C045856:ginkgolide B