Neutrophil-derived leukotriene B4 is required for inflammatory arthritis.
Neutrophil-derived leukotriene B4 is required for inflammatory arthritis.
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炎性关节炎需要中性粒细胞的白细胞B4。
DOI：
10.1084/jem.20052371
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发表时间：
2006-04-17
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中性粒细胞作为对入侵病原体的急性先天免疫应答的先锋。中性粒细胞在自身免疫性炎症的部位也很丰富，如类风湿关节，尽管它们的病理生理作用还不完全确定，相关的效应子功能仍然不清楚。在关节炎的K/BxN血清转移模型中使用遗传学和药理学方法，我们发现自身抗体驱动的糜烂性滑膜炎严重依赖于白三烯的产生，更具体地说，依赖于白三烯B4（LTB 4），用于疾病诱导和延续。追求这种介质的细胞来源，我们发现，通过重建实验，肥大细胞是一种来源的白三烯，而关节炎的易感性可以恢复到白三烯缺乏小鼠通过静脉注射野生型中性粒细胞。这些实验证明了LTB 4在炎症性关节炎中的非冗余作用，并定义了参与协调滑膜疹的中性粒细胞介导物。
Neutrophils serve as a vanguard of the acute innate immune response to invading pathogens. Neutrophils are also abundant at sites of autoimmune inflammation, such as the rheumatoid joint, although their pathophysiologic role is incompletely defined and relevant effector functions remain obscure. Using genetic and pharmacologic approaches in the K/BxN serum transfer model of arthritis, we find that autoantibody-driven erosive synovitis is critically reliant on the generation of leukotrienes, and more specifically on leukotriene B4 (LTB4), for disease induction as well as perpetuation. Pursuing the cellular source for this mediator, we find via reconstitution experiments that mast cells are a dispensable source of leukotrienes, whereas arthritis susceptibility can be restored to leukotriene-deficient mice by intravenous administration of wild-type neutrophils. These experiments demonstrate a nonredundant role for LTB4 in inflammatory arthritis and define a neutrophil mediator involved in orchestrating the synovial eruption.