Cytosolic phospholipase A2α-deficient mice are resistant to collagen-induced arthritis

被引:131
作者
Hegen, M
Sun, LH
Uozumi, N
Kume, K
Goad, ME
Nickerson-Nutter, CL
Shimizu, T [1 ]
Clark, JD
机构
[1] Univ Tokyo, Fac Med, Dept Biochem & Mol Biol, Bunkyo Ku, Tokyo 1130033, Japan
[2] Univ Tokyo, CREST, Tokyo 1130033, Japan
[3] Wyeth Ayerst Res, Musculoskeletal Sci, Cambridge, MA 02140 USA
关键词
inflammation; autoimmunity; rheumatoid arthritis; lipid mediators; gene targeting;
D O I
10.1084/jem.20030016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Pathogenic mechanisms relevant to rheumatoid arthritis occur in the mouse model of collagen-induced arthritis (CIA). Cytosolic phospholipase A(2)alpha (cPLA(2)alpha) releases arachidonic acid from cell membranes to initiate the production of prostaglandins and leukotrienes. These inflammatory mediators have been implicated in the development of CIA. To test the hypothesis that cPLA(2)alpha plays a key role in the development of CIA, we backcrossed cPLA(2)alpha-deficient mice on the DBA/1LacJ background that is susceptible to CIA. The disease severity scores and the incidence of disease were markedly reduced in cPLA(2)alpha-deficient mice compared with wildtype littermates. At completion of the study, > 90% of the wild-type mice had developed disease whereas none of the cPLA(2)alpha-deficient mice had more than one digit inflamed. Furthermore, visual disease scores correlated with severity of disease determined histologically. Pannus formation, articular fibrillation, and ankylosis were all dramatically reduced in the cPLA(2)alpha-deficient mice. Although the disease scores differed significantly between cPLA(2)alpha mutant and wild-type mice, anti-collagen antibody levels were similar in the wild-type mice and mutant littermates. These data demonstrate the critical role of cPLA(2)alpha in the pathogenesis of CIA.
引用
收藏
页码:1297 / 1302
页数:6
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