Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia: Elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival
Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia: Elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival
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DOI：
10.1128/iai.65.4.1139-1146.1997
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发表时间：
1997-04-01
影响因子：
3.1
通讯作者：
Standiford, TJ
中科院分区：
文献类型：
--
作者：
BrougHolub, E;Toews, GB;Standiford, TJ
为探讨肺泡巨噬细胞(AM)在小鼠革兰氏阴性细菌性肺炎中的体内作用，用气管内给药(I.T.)清除AM。二氯亚甲基二膦酸脂质体的给药。随后，耗尽AM的小鼠被I.T.感染。用100个肺炎克雷伯氏菌CFU，并评估AM耗竭对存活、细菌清除和中性粒细胞(PMN)募集的影响，结果表明，AM耗竭显著降低了存活率，感染后第3天的致死率为100%，而对照组的长期存活率为100%。死亡率增加的同时，肺和血浆中肺炎克雷伯菌CFU的数量分别增加了20~27倍和3~10倍。与未耗竭的动物相比，这种细菌清除减少不是由于PMN募集受损所致；相反，肺炎克雷伯菌感染后48h，肺泡灌洗液中PMN募集数是对照组的7倍，PMN浸润增加，肺组织匀浆肿瘤坏死因子-α(TNF-α)和巨噬细胞炎性蛋白2(MIP-2)水平分别增加3倍和10倍。我们的研究表明，在感染前2小时，中和TNF-α或MIP-2，使浸润性PMN数量分别减少41.6%和64.2%，表明这些细胞因子介导PMN在感染肺内流入，而不是由被招募的PMN本身产生。第一次，AM在控制和清除肺炎克雷伯氏菌细菌方面的相对重要性。
To study the in vivo role of alveolar macrophages (AM) in gram-negative bacterial pneumonia in mice, AM were eliminated by the intratracheal (i.t.) administration of dichloromethylene diphosphonate encapsulated liposomes. Subsequently, the AM-depleted mice were infected i.t. with 100 CFU of Klebsiella pneumoniae, and the effects of AM depletion on survival, bacterial clearance, and neutrophil (polymorphonuclear leukocyte [PMN]) recruitment were assessed, It was shown that depletion of AM decreases survival dramatically, with 100% lethality at day 3 postinfection, versus 100% long-term survival in the control group, This increased mortality was accompanied by 20- to 27- and 3- to 10-fold increases in the number of K. pneumoniae CFU in lung and plasma, respectively, compared to those in nondepleted animals, This decreased bacterial clearance was not due to an impaired PMN recruitment; on the contrary, the K. pneumoniae-induced PMN recruitment in AM-depleted lungs was sevenfold greater 48 h postinfection than that in control infected lungs, Together with an increased PMN infiltration, 3- and 10-fold increases in lung homogenate tumor necrosis factor alpha (TNF-a) and macrophage inflammatory protein 2 (MIP-2) levels, respectively, were measured, Neutralization of tnf-alpha or MIP-2, 2 h before infection, reduced the numbers of infiltrating PMN by 41.6 and 64.2%, respectively, indicating that these cytokines mediate PMN influx in infected lungs, rather then just being produced by the recruited PMN themselves, Our studies demonstrate, for the first time, the relative importance of the AM in the containment and clearance of bacteria in the setting of Klebsiella pneumonia.