Proinflammatory lipoxygenase products from peripheral mononuclear cells in patients with rheumatoid arthritis.
The formation of 5-lipoxygenase products (5-hydroxyeicosatetraenoic acid [5-HETE], leukotriene B4 [LTB4], and leukotriene C4 [LTC4]) by polymorphonuclear and mononuclear leukocytes isolated from peripheral blood of patients with rheumatoid arthritis was evaluated and compared with the data obtained from a group of control subjects. Although the levels of arachidonic acid metabolites via 5-lipoxygenase pathway by stimulated polymorphonuclear cells were comparable between patients and controls, mononuclear leukocytes from patients synthesized, when stimulated, significantly greater amounts of 5-HETE, LTB4, and LTC4 than did cells isolated from normal subjects. In addition, the release of superoxide anion, stimulated by either a particulate or a soluble stimulus, was increased in mononuclear cells from patients. The enhanced capacity of peripheral mononuclear leukocytes isolated from patients with rheumatoid arthritis to generate proinflammatory metabolites of arachidonic acid and oxygenated species with bactericidal and tissue-damaging properties may contribute to the pathogenesis of this complex disease.
Colli
S
S
E. Grossi Paoletti Center, Institute of Pharmacological Sciences, University of Milan, Italy.
Caruso
D
D
Stragliotto
E
E
Morazzoni
G
G
Aletti
A
A
Galli
G
G
Canesi
B A
BA
Tremoli
E
E
D001172:Arthritis, Rheumatoid / Q000097:blood*; D000001:Calcimycin / Q000494:pharmacology; D002449:Cell Aggregation; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D007975:Leukotriene B4 / Q000097:blood*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D010587:Phagocytosis; D013189:SRS-A / Q000097:blood*; D013481:Superoxides / Q000097:blood
D006893:Hydroxyeicosatetraenoic Acids; D013189:SRS-A; D013481:Superoxides; D007975:Leukotriene B4; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D009240:N-Formylmethionine Leucyl-Phenylalanine