Enhanced capacity for release of leucotriene B4 by neutrophils in rheumatoid arthritis.
The calcium dependent metabolism of endogenous arachidonic acid (AA) was investigated in 17 patients with rheumatoid arthritis during treatment with dextropropoxyphene alone and in 25 healthy volunteers. Incorporation of [1-14C]AA into intracellular phospholipids of purified neutrophils was achieved by incubation until steady state before activation with ionophore A23187. Analysis of extracellular metabolites was performed by extraction, thin layer chromatography, autoradiography, and laser densitometry. The patients showed a twofold increase in the total capacity for oxidation of AA. Release of leucotriene B4 (LTB4) and its omega oxidation products, 20-OH LTB4 and 20-COOH LTB4, was 29%, range 11-48%, in patients compared with 8%, range 4-12%, in healthy volunteers. Total amounts of radioactivity released and the specific activity of LTB4, as assessed by high pressure liquid chromatography, were equal in experimental and control groups. The demonstrated increased capacity for metabolism of AA to the major proinflammatory metabolite, LTB4, via the 5-lipoxygenase pathway may contribute to perpetuation of inflammation and to tissue destruction in rheumatoid arthritis.
Elmgreen
J
J
Department of Rheumatology TTA, Rigshopitalet, Copenhagen NV, Denmark.
Nielsen
O H
OH
Ahnfelt-Rønne
I
I
D000328:Adult; D000368:Aged; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood*; D000001:Calcimycin / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
D001095:Arachidonic Acids; D007975:Leukotriene B4; D016718:Arachidonic Acid; D000001:Calcimycin