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首页> 外文期刊>Infection and immunity >5-Lipoxygenase Reaction Products Modulate Alveolar Macrophage Phagocytosis of Klebsiella pneumoniae
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5-Lipoxygenase Reaction Products Modulate Alveolar Macrophage Phagocytosis of Klebsiella pneumoniae

机译：5-脂氧合酶反应产物调节肺炎克雷伯菌肺泡巨噬细胞吞噬

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The leukotrienes are potent lipid mediators of inflammation formed by the 5-lipoxygenase-catalyzed oxidation of arachidonic acid. Although the effects of leukotrienes on neutrophil chemotaxis and activation have been established, their role in modulating innate host defense mechanisms is poorly understood. In a previous study (M. Bailie, T. Standiford, L. Laichalk, M. Coffey, R. Strieter, and M. Peters-Golden, J. Immunol. 157:5221–5224, 1996), we used 5-lipoxygenase knockout mice to establish a critical role for endogenous leukotrienes in pulmonary clearance and alveolar macrophage phagocytosis ofKlebsiella pneumoniae. In the present study, we investigated the role of specific endogenous leukotrienes in phagocytosis of K. pneumoniae and explored the possibility that exogenous leukotrienes could restore phagocytosis in alveolar macrophages with endogenous leukotriene synthesis inhibition and enhance this process in leukotriene-competent cells. Rat alveolar macrophages produced leukotriene B4 (LTB4), LTC4, and 5-hydoxyeicosatetraenoic acid (5-HETE) during the process of phagocytosis, and the inhibition of endogenous leukotriene synthesis with zileuton and MK-886 dramatically attenuated phagocytosis. We also observed a reduction in phagocytosis when we treated alveolar macrophages with antagonists to the plasma membrane receptors for either LTB4, cysteinyl-leukotrienes, or both. In leukotriene-competent cells, LTC4 augmented phagocytosis to the greatest extent, followed by 5-HETE and LTB4. These 5-lipoxygenase reaction products demonstrated similar relative abilities to reconstitute phagocytosis in zileuton-treated rat alveolar macrophages and in alveolar macrophages from 5-lipoxygenase knockout mice. We conclude that endogenous synthesis of all major 5-lipoxygenase reaction products plays an essential role in phagocytosis. The restorative and pharmacologic effects of LTC4, LTB4, and 5-HETE may provide a basis for their exogenous administration as an adjunctive treatment for patients with gram-negative bacterial pneumonia.
机译：白三烯是由5-脂氧合酶催化的花生四烯酸氧化形成的炎症的有效脂质介体。尽管已经建立了白三烯对嗜中性粒细胞趋化性和活化的影响，但人们对它们在调节先天宿主防御机制中的作用知之甚少。在先前的研究中（M. Bailie，T。Standiford，L.Laichalk，M。Coffey，R。Strieter和M.Peters-Golden，J.Immunol。157：5221–5224，1996），我们使用了5-脂氧合酶基因敲除小鼠对内源性白三烯在肺炎克雷伯菌肺炎清除和肺泡巨噬细胞吞噬中起关键作用。在本研究中，我们调查了特定内源性白三烯在 K吞噬中的作用。肺炎，并探讨了外源性白三烯可以恢复具有内源性白三烯合成抑制作用的肺泡巨噬细胞吞噬作用并增强白三烯功能细胞中这一过程的可能性。大鼠肺泡巨噬细胞在形成过程中产生白三烯B 4 （LTB 4 ），LTC 4 和5-羟二十碳四烯酸（5-HETE）。吞噬作用，以及用齐留通和MK-886抑制内源性白三烯合成会大大减弱吞噬作用。当用LTB 4 ，半胱氨酰-白三烯或两者的质膜受体拮抗剂处理肺泡巨噬细胞时，我们还观察到吞噬作用的降低。在具有白三烯能力的细胞中，LTC 4 增强了吞噬作用，其次是5-HETE和LTB 4 。这些5-脂氧合酶反应产物在齐勒通治疗的大鼠肺泡巨噬细胞和5-脂氧合酶敲除小鼠的肺泡巨噬细胞中具有相似的相对吞噬能力。我们得出结论，所有主要的5-脂氧合酶反应产物的内源性合成在吞噬作用中起着至关重要的作用。 LTC 4 ，LTB 4 和5-HETE的修复和药理作用可能为革兰氏阴性细菌性肺炎的辅助治疗提供外源性给药基础。

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