Conversion of endogenous arachidonic acid to 5,15-diHETE and lipoxins by polymorphonuclear cells from patients with rheumatoid arthritis.
The conversion of endogenous arachidonic acid (AA) by polymorphonuclear cells (PMN) from patients with rheumatoid arthritis (RA) was studied before (D0) and one day (D1) after antiinflammatory drug therapy. The biosynthesis of 5,15-diHETE and lipoxins (LXS), were investigated ex vivo, after PMN stimulation by ionophore A23187 without exogenous addition of 15-HETE. The eicosanoids were resolved by RP-HPLC and simultaneously detected at 246 and 302 nm respectively. Large amounts of 5,15-diHETE (50 to 400 ng/10(7) PMN) and significant levels of LXS (from 2 to 20 ng/10(7) PMN) were produced with individual differences between donors. Metabolite levels varied between patients but this work showed for the first time a linear relationship between the amounts of 5,15-diHETE and LXS. Moreover LXS production after treatment may be related to long-term clinical improvement of patients.
Thomas
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E
Centre de Recherches INSERM, Montpellier, France.
Leroux
J L
JL
Blotman
F
F
Chavis
C
C
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D044045:Lipoxins; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D000893:Anti-Inflammatory Agents; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; C040527:lipoxin A4; D016718:Arachidonic Acid; D000001:Calcimycin; C034922:5,15-dihydroxy-6,8,11,13-eicosatetraenoic acid; C042651:lipoxin B4; C044354:lipoxin A5; C044355:lipoxin B5; D015118:Eicosapentaenoic Acid