Gregory S H, Sagnimeni A J, Wing E J
Department of Medicine, University of Pittsburgh Medical Center, PA 15213, USA.
J Immunol. 1996 Sep 15;157(6):2514-20.
The critical role of the liver in the resolution of systemic bacterial infections is well documented. In the case of Listeria monocytogenes, approximately 60% of bacteria inoculated i.v. into mice are recovered in the liver at 10 min after infection. Here we report that the Listeria recovered at 10 min were distributed equally among the hepatocyte and nonparenchymal liver cell populations. The majority (>/= 75%) of these organisms were bound extracellularly as judged by their sensitivity to gentamicin. In contrast, >/= 93% of Listeria recovered in the liver at 6 h were located within hepatocytes. The listerial burden of the liver decreased 0.5 to 1.0 log, between 10 min and 6 h after infection. This decrease correlated with a sevenfold increase in the percentage of neutrophils that constituted the nonparenchymal cell population. Mice rendered neutrophil deficient by pretreatment with anti-granulocyte (RB6-8C5) mAb exhibited a significant increase (>300%) rather than a decrease in liver Listeria and a marked increase in hepatocyte damage. Similarly, neutrophil-deficient mice exhibited a reduced capacity to eliminate Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus that were cleared by the liver and bound extracellularly to hepatocytes and nonparenchymal cells. These findings document the crucial role of immigrating neutrophils in nonspecific host defenses to systemic bacterial infections expressed within the liver.
肝脏在全身性细菌感染消退过程中的关键作用已有充分记载。就单核细胞增生李斯特菌而言，静脉注射到小鼠体内的细菌，在感染后10分钟时，约60%可在肝脏中找到。我们在此报告，感染后10分钟时回收的李斯特菌在肝细胞和肝非实质细胞群体中分布均匀。根据这些细菌对庆大霉素的敏感性判断，其中大多数（≥75%）是细胞外结合的。相比之下，感染后6小时在肝脏中回收的李斯特菌≥93%位于肝细胞内。感染后10分钟至6小时之间，肝脏中的李斯特菌负荷下降了0.5至1.0个对数级。这种下降与构成非实质细胞群体的中性粒细胞百分比增加了7倍相关。用抗粒细胞（RB6-8C5）单克隆抗体预处理使中性粒细胞缺乏的小鼠，肝脏中的李斯特菌显著增加（>300%）而非减少，且肝细胞损伤明显增加。同样，中性粒细胞缺乏的小鼠清除经肝脏清除并细胞外结合到肝细胞和非实质细胞的大肠杆菌、肺炎克雷伯菌和金黄色葡萄球菌的能力降低。这些发现证明了迁移的中性粒细胞在肝脏内表达的全身性细菌感染的非特异性宿主防御中的关键作用。
