Silva Reinaldo C, Landgraf Maristella A, Hiyane Meire I, Pacheco-Silva Alvaro, Câmara Niels O, Landgraf Richardt G
Laboratorio de Imunologia Clínica e Experimental, Departamento de Nefrologia, Universidade Federal de São Paulo, São Paulo, Brazil.
Cell Physiol Biochem. 2010;26(3):319-26. doi: 10.1159/000320555. Epub 2010 Aug 24.
It has been well-documented that leukotrienes (LTs) are released in allergic lung inflammation and that they participate in the physiopathology of asthma. A role for LTs in innate immunity has recently emerged: Cys-LTs were shown to enhance FcgammaR-mediated phagocytosis by alveolar macrophages (AMs). Thus, using a rat model of asthma, we evaluated FcgammaR-mediated phagocytosis and killing of Klebsiella pneumoniae by AMs. The effect of treatment with a cys-LT antagonist (montelukast) on macrophage function was also investigated. Male Wistar rats were immunized twice with OVA/alumen intraperitoneally and challenged with OVA aerosol. After 24 h, the animals were killed, and the AMs were obtained by bronchoalveolar lavage. Macrophages were cultured with IgG-opsonized red blood cells (50:1) or IgG-opsonized K. pneumoniae (30:1), and phagocytosis or killing was evaluated. Leukotriene C(4) and nitric oxide were quantified by the EIA and Griess methods, respectively. The results showed that AMs from sensitized and challenged rats presented a markedly increased phagocytic capacity via FcgammaR (10X compared to controls) and enhanced killing of K. pneumoniae (4X higher than controls). The increased phagocytosis was inhibited 15X and killing 3X by treatment of the rats with montelukast, as compared to the non-treated group. cys-LT addition increased phagocytosis in control AMs but had no effect on macrophages from allergic lungs. Montelukast reduced nitric oxide (39%) and LTC(4) (73%). These results suggest that LTs produced during allergic lung inflammation potentiate the capacity of AMs to phagocytose and kill K. pneumonia via FcgammaR.
大量文献记载，白三烯（LTs）在过敏性肺部炎症中释放，并参与哮喘的病理生理过程。最近，LTs在天然免疫中的作用逐渐显现：半胱氨酰白三烯（Cys-LTs）可增强肺泡巨噬细胞（AMs）介导的FcγR吞噬作用。因此，我们使用哮喘大鼠模型，评估AMs介导的FcγR对肺炎克雷伯菌的吞噬和杀伤作用。同时，研究了半胱氨酰白三烯拮抗剂（孟鲁司特）对巨噬细胞功能的影响。雄性Wistar大鼠腹腔内注射卵清蛋白/明矾免疫两次，然后用卵清蛋白气雾剂激发。24小时后，处死动物，通过支气管肺泡灌洗获取AMs。巨噬细胞与IgG调理的红细胞（50:1）或IgG调理的肺炎克雷伯菌（30:1）共培养，评估吞噬或杀伤作用。分别采用酶免疫分析（EIA）和格里斯方法（Griess method）定量白三烯C4（Leukotriene C(4)）和一氧化氮。结果显示，致敏和激发大鼠的AMs通过FcγR呈现出显著增强的吞噬能力（比对照组高10倍），对肺炎克雷伯菌的杀伤作用增强（比对照组高4倍）。与未治疗组相比，孟鲁司特治疗大鼠可使吞噬作用抑制15倍，杀伤作用抑制3倍。添加半胱氨酰白三烯可增加对照AMs的吞噬作用，但对过敏性肺巨噬细胞无影响。孟鲁司特可降低一氧化氮（39%）和白三烯C4（73%）。这些结果表明，过敏性肺部炎症期间产生的LTs可增强AMs通过FcγR吞噬和杀伤肺炎克雷伯菌的能力。
