Knapp Sylvia, Leemans Jaklien C, Florquin Sandrine, Branger Judith, Maris Nico A, Pater Jennie, van Rooijen Nico, van der Poll Tom
Laboratory of Experimental Internal Medicine, Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
Am J Respir Crit Care Med. 2003 Jan 15;167(2):171-9. doi: 10.1164/rccm.200207-698OC. Epub 2002 Sep 25.
Alveolar macrophages (AMs) are considered major effector cells in host defense against respiratory tract infections by virtue of their potent phagocytic properties. In addition, AMs may regulate the host inflammatory response to infection by production of cytokines and by their capacity to phagocytose apoptotic polymorphonuclear cells (PMNs). To elucidate the in vivo contribution of AM to host defense against pneumococcal pneumonia, we depleted mice of AMs via pulmonary application of liposomal dichloromethylene-bisphosphonate (AM- mice) before inoculation with Streptococcus pneumoniae; control mice received saline (AM+sal) or liposomal phosphate-buffered saline (AM+lip) before bacterial inoculation. AM- mice displayed a significantly higher mortality compared with AM+ control mice, whereas bacterial clearance did not differ. Poor outcome of AM- mice was accompanied by a pronounced increase of local proinflammatory cytokine production as well as strongly elevated and prolonged pulmonary PMN accumulation. Closer examination of infiltrating PMN in AM- mice disclosed high proportions of apoptotic and secondary necrotic cells, reflecting the lack of efficient clearance mechanisms in the absence of AMs. Furthermore, caspase-3 staining showed only slightly higher activity in AM- mice, arguing against accelerated apoptosis per se. These data suggest that AMs are indispensable in the host response to pneumococcal pneumonia by means of their capacity to modulate inflammation, possibly via elimination of apoptotic PMNs.
肺泡巨噬细胞（AMs）凭借其强大的吞噬特性，被认为是宿主抵御呼吸道感染的主要效应细胞。此外，AMs可通过产生细胞因子以及吞噬凋亡多形核细胞（PMNs）的能力来调节宿主对感染的炎症反应。为阐明AMs在宿主抵御肺炎球菌肺炎中的体内作用，我们在接种肺炎链球菌之前，通过肺部应用脂质体二氯亚甲基二膦酸盐使小鼠的AMs耗竭（AMs缺陷小鼠）；对照小鼠在细菌接种前接受生理盐水（AMs+生理盐水组）或脂质体磷酸盐缓冲盐水（AMs+脂质体组）。与AMs+对照小鼠相比，AMs缺陷小鼠的死亡率显著更高，而细菌清除率并无差异。AMs缺陷小鼠预后不良伴随着局部促炎细胞因子产生的明显增加以及肺部PMN积累的强烈升高和持续时间延长。对AMs缺陷小鼠中浸润的PMN进行更仔细检查发现，凋亡和继发性坏死细胞比例很高，这反映出在没有AMs的情况下缺乏有效的清除机制。此外，caspase-3染色显示AMs缺陷小鼠中的活性仅略高，这表明并非凋亡本身加速。这些数据表明，AMs通过其调节炎症的能力，可能是通过清除凋亡的PMN，在宿主对肺炎球菌肺炎的反应中不可或缺。
