Collagen-induced arthritis is reduced in 5-lipoxygenase-activating protein-deficient mice.
Collagen-induced arthritis is reduced in 5-lipoxygenase-activating protein-deficient mice.
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DOI：
10.1084/jem.185.6.1123
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发表时间：
1997-03-17
影响因子：
15.3
通讯作者：
McNeish, J D
中科院分区：
文献类型：
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作者：
Griffiths, R J;Smith, M A;Roach, M L;Stock, J L;Stam, E J;Milici, A J;Scampoli, D N;Eskra, J D;Byrum, R S;Koller, B H;McNeish, J D
DBA/1 小鼠胶原诱导的关节炎是人类类风湿性关节炎的实验模型。为了研究白三烯在这种疾病发病机制中的作用，我们从该小鼠品系中培育出胚胎干（ES）细胞。在此，我们报告通过 ES 细胞中的基因靶向导致 5-脂氧合酶激活蛋白 (FLAP) 缺陷的 DBA/1 小鼠能够正常发育和生长。在这些小鼠的腹膜腔中，酵母聚糖刺激的白三烯的产生是检测不到的，而它们却产生了大量的前列腺素。 FLAP 缺陷小鼠对酵母聚糖的炎症反应减少。与野生型或杂合子动物相比，FLAP 缺陷小鼠中胶原蛋白诱导的关节炎的严重程度显着降低。这并不是由于免疫抑制作用，因为野生型和 FLAP 缺陷小鼠的抗胶原抗体水平相似。这些数据表明白三烯在小鼠的急性和慢性炎症反应中发挥着重要作用。
Collagen-induced arthritis in the DBA/1 mouse is an experimental model of human rheumatoid arthritis. To examine the role of leukotrienes in the pathogenesis of this disease, we have developed embryonic stem (ES) cells from this mouse strain. Here, we report that DBA/1 mice made deficient in 5-lipoxygenase-activating protein (FLAP) by gene targeting in ES cells develop and grow normally. Zymosan-stimulated leukotriene production in the peritoneal cavity of these mice is undetectable, whereas they produce substantial amounts of prostaglandins. The inflammatory response to zymosan is reduced in FLAP-deficient mice. The severity of collagen-induced arthritis in the FLAP-deficient mice was substantially reduced when compared with wild-type or heterozygous animals. This was not due to an immunosuppressive effect, because anti-collagen antibody levels were similar in wild-type and FLAP-deficient mice. These data demonstrate that leukotrienes play an essential role in both the acute and chronic inflammatory response in mice.