Tsai W C, Strieter R M, Wilkowski J M, Bucknell K A, Burdick M D, Lira S A, Standiford T J
Department of Medicine, University of Michigan Medical School, Ann Arbor 48109, USA.
J Immunol. 1998 Sep 1;161(5):2435-40.
A vigorous host response is required to effectively clear pathogenic bacteria from the lungs and is dependent upon the recruitment and activation of neutrophils and macrophages. A family of chemotactic cytokines, referred to as chemokines, have been shown to participate in this complex protective response. In this study, we assessed the role of the C-X-C chemokine KC in lung antibacterial host defense using wild-type (wt) B6D2 mice or transgenic mice that had been bred on a B6D2 background expressing KC under the control of a Clara cell-specific promoter within the lung. The administration of Klebsiella pneumoniae to both wt and KC-transgenic mice resulted in a time-dependent expression of KC protein within the lung that peaked at 24 to 48 h postinoculation. When infected with K. pneumoniae, the KC-transgenic mice showed a striking improvement in survival compared with wt control mice. This improved survival was due to an increase in bacterial clearance, which occurred in association with a vigorous recruitment of neutrophils in the KC-transgenic mice compared with their wt control counterparts. No differences in the lung levels of the specific cytokines TNF-alpha, IFN-gamma, IL-12, and IL-10 were noted. However, inducible macrophage inflammatory protein-2 levels were significantly decreased in the KC-transgenic mice compared with the wt mice. This study indicates that the compartmentalized overexpression of KC in vivo results in increased lung bacterial clearance and improved survival, which occurs in association with enhanced polymorphonuclear leukocyte influx to the lung.
要有效地清除肺部的病原菌，需要强烈的宿主反应，这依赖于中性粒细胞和巨噬细胞的募集与激活。一类趋化细胞因子，即趋化因子，已被证明参与了这种复杂的保护反应。在本研究中，我们使用野生型（wt）B6D2小鼠或在B6D2背景上培育的转基因小鼠来评估C-X-C趋化因子KC在肺部抗菌宿主防御中的作用，这些转基因小鼠在肺内克拉拉细胞特异性启动子的控制下表达KC。给wt小鼠和KC转基因小鼠注射肺炎克雷伯菌后，肺内KC蛋白的表达呈时间依赖性，在接种后24至48小时达到峰值。与wt对照小鼠相比，感染肺炎克雷伯菌时，KC转基因小鼠的存活率显著提高。存活率的提高归因于细菌清除率的增加，这与KC转基因小鼠相对于其wt对照小鼠中性粒细胞的大量募集有关。未观察到特异性细胞因子肿瘤坏死因子-α、干扰素-γ、白细胞介素-12和白细胞介素-10在肺内水平的差异。然而，与wt小鼠相比，KC转基因小鼠中诱导型巨噬细胞炎性蛋白-2水平显著降低。本研究表明，体内KC的局部过表达导致肺细菌清除率增加和存活率提高，这与多形核白细胞向肺内的流入增加有关。
