Sugawara Isamu, Udagawa Tadashi, Yamada Hiroyuki
Mycobacterial Reference Center, The Research Institute of Tuberculosis, Tokyo 204-0022, Japan.
Infect Immun. 2004 Mar;72(3):1804-6. doi: 10.1128/IAI.72.3.1804-1806.2004.
To understand the role of neutrophils in the development of rat tuberculosis in vivo, we utilized lipopolysaccharide (LPS)-induced neutrophilia in the lungs. LPS (50 micro g/ml) was administered intratracheally to male Fischer rats. Rats were then infected with Mycobacterium tuberculosis by an airborne route. Intratracheal injection of LPS significantly blocked the development of pulmonary granulomas and significantly reduced pulmonary CFU (P < 0.01). LPS treatment with amphotericin B (an LPS inhibitor) or neutralizing anti-rat neutrophil antibody reversed the development of pulmonary lesions. LPS-induced transient neutrophilia prevented early mycobacterial infection. The timing of LPS administration was important. When given intratracheally at least 10 days after aerial infection, LPS did not prevent development of tuberculosis. Neutrophils obtained by bronchoalveolar lavage killed M. tuberculosis cells. These results indicate clearly that neutrophils participate actively in defense against early-phase tuberculosis.
为了解中性粒细胞在大鼠体内结核发生发展中的作用,我们利用脂多糖(LPS)诱导肺部中性粒细胞增多。将LPS(50μg/ml)经气管内给予雄性Fischer大鼠。然后通过空气传播途径用结核分枝杆菌感染大鼠。气管内注射LPS显著阻断了肺部肉芽肿的形成,并显著降低了肺部菌落形成单位(P<0.01)。用两性霉素B(一种LPS抑制剂)或中和抗大鼠中性粒细胞抗体进行LPS处理可逆转肺部病变的发展。LPS诱导的短暂性中性粒细胞增多可预防早期分枝杆菌感染。LPS给药的时机很重要。在空气传播感染后至少10天经气管内给予LPS时,LPS并不能预防结核病的发生。通过支气管肺泡灌洗获得的中性粒细胞可杀死结核分枝杆菌细胞。这些结果清楚地表明,中性粒细胞积极参与早期结核病的防御。