Tomioka H, Sato K, Shimizu T, Akaki T
Department of Microbiology and Immunology, Shimane Medical University, Japan.
Kekkaku. 1998 Feb;73(2):71-6.
In order to know profiles of the antimicrobial action of some microbicidal effector molecules against Mycobacterium avium complex (MAC) and M. tuberculosis (MTB), profiles of collaborating effects among reactive nitrogen intermediates (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) were studied, RNI and FFA exerted synergistic effects in killing MAC and MTB, while the combination of ROI (H2O2-mediated halogenation system) with FFA conversely caused antagonism. The combination of RNI with ROI displayed additive effects in killing MTB, whereas the same combination showed antagonistic effects against MAC. Murine peritoneal macrophages (M phi s) produced and/or released these three antimicrobial effectors in the order ROI, FFA, and RNI in response to cellular stimulation induced by their contact with MAC or MTB organisms. These findings indicate that the collaborating effect of RNI with FFA is crucial for M phi-mediated intracellular killing of MAC and MTB. Secondly, we examined the modes of bacterial growth of MAC and MTB in murine peritoneal M phi s and A-549 type II alveolar epithelial cell line. The growth rate of these organisms was much larger in A-549 cells than in M phi s. In addition, the growth rate of high-virulence MAC (N-260 strain) was significantly larger than that of low-virulence MAC (N-444 strain), when they were residing in M phi or A-549 cells. Although a high virulence MTB (strain Kurono) also showed much more rapid growth in M phi s than did low-virulence MTB (strain H37Ra), such a phenomenon was not observed for their intracellular growth in A-549 cells. MTB exhibited strong cytotoxic effects against M phi s but not against A-549 cells when resided in these cells. On the other hand, MAC organisms did not cause cytotoxicity even in M phi s. Although MAC and MTB infections caused significant increase in RNI production by M phi s but not by A-549 cells, there was no significant relationship between the degree of M phi RNI production by a given mycobacterial organism and its virulence. These findings indicate some important roles of type II alveolar epithelial cells as a target cell for primary invasion and transient growth of mycobacterial organisms in the host lungs.
为了解某些杀菌效应分子对鸟分枝杆菌复合群（MAC）和结核分枝杆菌（MTB）的抗菌作用概况，研究了活性氮中间体（RNI）、游离脂肪酸（FFA）和活性氧中间体（ROI）之间的协同作用概况。RNI和FFA在杀灭MAC和MTB方面发挥协同作用，而ROI（H2O2介导的卤化系统）与FFA的组合则产生拮抗作用。RNI与ROI的组合在杀灭MTB时表现出相加作用，而相同组合对MAC则表现出拮抗作用。小鼠腹腔巨噬细胞（M phi s）在与MAC或MTB生物体接触诱导的细胞刺激下，按ROI、FFA和RNI的顺序产生和/或释放这三种抗菌效应分子。这些发现表明，RNI与FFA的协同作用对于M phi介导的细胞内杀灭MAC和MTB至关重要。其次，我们研究了MAC和MTB在小鼠腹腔M phi s和A - 549 II型肺泡上皮细胞系中的细菌生长模式。这些生物体在A - 549细胞中的生长速度比在M phi s中快得多。此外，高毒力MAC（N - 260菌株）在M phi或A - 549细胞中时，其生长速度明显高于低毒力MAC（N - 444菌株）。尽管高毒力MTB（Kurono菌株）在M phi s中的生长也比低毒力MTB（H37Ra菌株）快得多，但在A - 549细胞中的细胞内生长情况未观察到这种现象。MTB在这些细胞中时，对M phi s表现出强烈的细胞毒性作用，但对A - 549细胞则无此作用。另一方面，MAC生物体即使在M phi s中也不会引起细胞毒性。尽管MAC和MTB感染导致M phi s而非A - 549细胞产生的RNI显著增加，但特定分枝杆菌生物体产生的M phi RNI程度与其毒力之间没有显著关系。这些发现表明II型肺泡上皮细胞作为宿主肺部分枝杆菌生物体初次入侵和短暂生长的靶细胞具有一些重要作用。
