Ramos B F, Zhang Y, Qureshi R, Jakschik B A
Washington University School of Medicine, Department of Pharmacology, St. Louis, MO 63110.
J Immunol. 1991 Sep 1;147(5):1636-41.
Mast cells are secretory cells strategically located in the vicinity of blood vessels where they can readily initiate and modulate various inflammatory processes, including plasma exudation and leukocyte infiltration. We have previously shown that 50% of the neutrophil influx during immune complex peritonitis in mice is due to mast cells. Eicosanoids are important mediators of various inflammatory processes including neutrophil infiltration. The possibility that mast cells are essential for the production of leukotrienes (LT) involved in the elicitation of neutrophils in immune complex peritonitis was investigated in mast cell-deficient, WBB6F1-W/WV, and normal, WBB6F(1-)+/+, mice. The time course and amounts of immunoreactive PGE2, 6-keto-PGF1 alpha, and TX3B2 released into the peritoneal exudates were similar in both sets of mice. LTB4 and LTC4 levels, however, were twofold higher in +/+ than in W/WV mice 2 h after stimulation. HPLC analysis of the peritoneal exudate confirmed the presence of leukotrienes. The 5-lipoxygenase inhibitor A-63162 blocked leukotriene production in a dose-dependent manner in both sets of mice. However, this compound caused a significant reduction (60%) of neutrophil infiltration only in WBB6F(1-)+/+ but not in the mast cell-deficient mice. Mast cell reconstitution of WBB6F1-W/WV mice restored the effect of A-63162 on PMN recruitment. These data suggest that mast cells in the vicinity of blood vessels are important for the synthesis of leukotrienes responsible for PMN recruitment.
肥大细胞是一种分泌细胞，主要分布在血管附近，在那里它们能够迅速启动并调节各种炎症过程，包括血浆渗出和白细胞浸润。我们之前已经表明，在小鼠免疫复合物性腹膜炎期间，50% 的中性粒细胞流入是由肥大细胞引起的。类花生酸是包括中性粒细胞浸润在内的各种炎症过程的重要介质。在肥大细胞缺陷型WBB6F1-W/WV小鼠和正常WBB6F(1-)+/+小鼠中，研究了肥大细胞对于免疫复合物性腹膜炎中引起中性粒细胞的白三烯（LT）产生是否必不可少。两组小鼠腹膜渗出液中释放的免疫反应性PGE2、6-酮-PGF1α和TX3B2的时间进程和量相似。然而，刺激后2小时，+/+小鼠的LTB4和LTC4水平比W/WV小鼠高两倍。腹膜渗出液的HPLC分析证实了白三烯的存在。5-脂氧合酶抑制剂A-63162在两组小鼠中均以剂量依赖性方式阻断白三烯的产生。然而，这种化合物仅在WBB6F(1-)+/+小鼠中导致中性粒细胞浸润显著减少（60%），而在肥大细胞缺陷型小鼠中则没有。WBB6F1-W/WV小鼠的肥大细胞重建恢复了A-63162对PMN募集的作用。这些数据表明，血管附近的肥大细胞对于负责PMN募集的白三烯的合成很重要。
