Impaired pulmonary inflammatory responses are a prominent feature of streptococcal pneumonia in mice with experimental emphysema
Impaired pulmonary inflammatory responses are a prominent feature of streptococcal pneumonia in mice with experimental emphysema
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DOI：
10.1164/rccm.2105111
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发表时间：
2003-03-01
影响因子：
24.7
通讯作者：
Tomoike, H
中科院分区：
文献类型：
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作者：
Inoue, S;Nakamura, H;Tomoike, H
关于慢性阻塞性肺疾病患者为什么容易受到细菌感染的原因知之甚少。利用肺气肿的动物模型，我们研究了细菌感染的炎症反应。对照组小鼠经腹腔感染肺炎链球菌（10（3）~ 10（7）cfu/只）后，无死亡。然而，患有肺气肿的小鼠以剂量依赖性方式死亡。感染后24小时检查支气管肺泡灌洗液，结果显示，与对照小鼠相比，肺气肿小鼠的总细胞数和嗜中性粒细胞数以及小鼠肿瘤坏死因子-α和巨噬细胞炎性蛋白-2浓度均显著降低。组织病理学检查显示，对照组小鼠肺泡充满炎性细胞和渗出物，而肺气肿组小鼠则无。感染后72小时，肺气肿小鼠血清细胞因子水平显著升高，且S。肺炎克雷伯氏菌在肺气肿小鼠的全肺组织和血液中均被检测到。这些发现表明，肺气肿小鼠的炎症反应在细菌感染部位受损，尽管菌血症，这加速了严重的全身炎症反应。因此，在实验性肺气肿的存在下，肺泡内而不是全身对细菌感染的免疫应答受损。
Little is known about why patients with chronic obstructive pulmonary disease are susceptible to bacterial infections. Using an animal model of pulmonary emphysema, we investigated the inflammatory responses to bacterial infection. After intratracheal infection with Streptococcus pneumoniae (10(3)-10(7) cfu/mouse), the control mice did not die. However, the mice with emphysema died in a dose-dependent manner. Bronchoalveolar lavage fluid, examined 24 hours after infection showed that the numbers of total cells and neutrophils, in addition to murine tumor necrosis factor-alpha and macrophage inflammatory protein-2 concentrations, were significantly less in the mice with emphysema compared with the control mice. Histopathologic findings revealed that the alveoli were filled with inflammatory cells and exudate in the control mice but not in the mice with emphysema. Seventy-two hours after infection, serum cytokine levels were significantly higher in the mice with emphysema, and significant numbers of S. pneumoniae were detected in both the whole lung tissues and the blood of mice with emphysema. These findings suggest that the inflammatory response in mice with emphysema was impaired at the site of bacterial infection despite the bacteremia, which accelerated severe systemic inflammatory responses. Accordingly, intra-alveolar but not systemic immune responses to bacterial infection were impaired in the presence of experimental emphysema.