ENHANCED INTERLEUKIN-8 RELEASE AND GENE-EXPRESSION IN MACROPHAGES AFTER EXPOSURE TO MYCOBACTERIUM-TUBERCULOSIS AND ITS COMPONENTS
ENHANCED INTERLEUKIN-8 RELEASE AND GENE-EXPRESSION IN MACROPHAGES AFTER EXPOSURE TO MYCOBACTERIUM-TUBERCULOSIS AND ITS COMPONENTS
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DOI：
10.1172/jci117702
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发表时间：
1995-02-01
影响因子：
15.9
通讯作者：
ROM, WN
中科院分区：
文献类型：
--
作者：
ZHANG, YH;BROSER, M;ROM, WN
结核分枝杆菌感染伴有急性和慢性炎性浸润性病变，并伴有肺组织坏死性肉芽肿。炎性细胞包括中性粒细胞、淋巴细胞和巨噬细胞。在分枝杆菌感染的动物和体外模型中，包括肿瘤坏死因子-α(肿瘤坏死因子-α)、干扰素-γ(干扰素-γ)和白介素1-β(IL-1β)在内的细胞因子参与肉芽肿性炎症。我们推测，白细胞介素8是一种对中性粒细胞和淋巴细胞有很强趋化作用的化学物质，在结核分枝杆菌或其成分暴露后，活化的肺泡巨噬细胞可能会释放出来，从而促进肉芽肿性肺部炎症。定量免疫分析显示，肺结核病患者巨噬细胞上清液和灌洗液中IL-8蛋白的释放明显高于正常对照组。此外，Northern blotts显示这些患者的巨噬细胞中IL-8mRNA的表达显著上调。结核分枝杆菌及其细胞壁成分脂阿拉伯甘露聚糖(LAM)、脂甘露聚糖(LM)和磷酸肌醇甘露糖苷(PIM)在体外可刺激肺泡巨噬细胞释放IL-8蛋白和表达IL-8，而去酰化的LAM则不能。抗肿瘤坏死因子-α和/或白介素1-α和白介素1-β的中和抗体阻断了83%的刺激。IL-8的合成和释放是巨噬细胞吞噬结核分枝杆菌后的早期反应。它的产生有助于吸引活动性感染的急性和慢性炎症细胞，从而参与病原体的遏制过程。
Mycobacterium tuberculosis infection is accompanied by acute and chronic inflammatory infiltrates associated with necrotizing granulomas in lung tissue. The cellular infiltrate is characterized by inflammatory cells which include neutrophils, lymphocytes, and macrophages. In animal and in vitro models of mycobacterial infection, cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) participate in granulomatous inflammation. We hypothesized that interleukin-8, a potent chemoattractant for neutrophils and lymphocytes, could be released by activated alveolar macrophages after exposure to M. tuberculosis or its components and contribute to granulomatous lung inflammation. A quantitative immunoassay revealed that IL-8 protein release was significantly elevated in supernatants of macrophages and in lavage fluid obtained from patients with pulmonary tuberculosis compared to normal controls. In addition, Northern blots demonstrated striking up-regulation of IL-8 mRNA in macrophages from these patients. M. tuberculosis and its cell wall components lipoarabinomannan (LAM), lipomannan (LM), and phosphoinositolmannoside (PIM) stimulated IL-8 protein release and mRNA expression in vitro from alveolar macrophages, but deacylated LAM did not. Neutralizing antibodies to TNF-alpha and/or IL-1-alpha and beta blocked 83% of the stimulation. IL-8 synthesis and release is an early response of macrophages after phagocytosis of M. tuberculosis. Its production serves to attract both acute and chronic inflammatory cells of active infection and thus participates in the process of containment of the pathogen.