Ben-David Itzhak, Price Sarah E, Bortz David M, Greineder Colin F, Cohen Samuel E, Bauer Amy L, Jackson Trachette L, Younger John G
Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Am J Respir Cell Mol Biol. 2005 Nov;33(5):476-82. doi: 10.1165/rcmb.2005-0053OC. Epub 2005 Jul 13.
To study the change in intrapulmonary bacterial growth rate over time during Gram-negative pneumonia, a two-hit model of recurrent bacterial aspiration was developed in mice. A mutant of Klebsiella pneumoniae was isolated that could be distinguished from the wild type when cultured on appropriate media. These strains were intranasally administered, 4 h apart, to mice whose lungs were quantitatively cultured 24 h later. The relative burden of each aspirated inoculum was determined, and, using the administered dose and the number of bacteria from each inoculum present at the end of the experiment, first-order growth constants for each inoculum were calculated. Results indicate that after an initial aspiration of this organism, subsequently aspirated bacteria proliferate more slowly. When two aspirations occurred 4 h apart, the bacteria aspirated first represented 96% of total lung burden at 24 h. The growth constant of the second inoculum was related to the magnitude of the first inoculum in an inverse, nonlinear fashion. When parallel experiments were performed in complement C3-deficient mice, no suppression of the second inoculum was noted, suggesting that early upregulation of antibacterial activity in the lung is a C3-mediated event.
为研究革兰氏阴性菌肺炎期间肺内细菌生长速率随时间的变化，在小鼠中建立了复发性细菌吸入的双打击模型。分离出一株肺炎克雷伯菌突变体，在合适的培养基上培养时可与野生型区分开来。将这些菌株间隔4小时经鼻给予小鼠，24小时后对小鼠肺部进行定量培养。确定每次吸入接种物的相对负荷，并根据给药剂量和实验结束时各接种物中的细菌数量，计算每个接种物的一级生长常数。结果表明，初次吸入这种细菌后，随后吸入的细菌增殖更缓慢。当间隔4小时进行两次吸入时，第一次吸入的细菌在24小时时占肺内总负荷的96%。第二次接种物的生长常数与第一次接种物的量呈反比的非线性关系。在补体C3缺陷小鼠中进行平行实验时，未观察到第二次接种物受到抑制，这表明肺内抗菌活性的早期上调是由C3介导的事件。
