Kajikawa Osamu, Frevert Charles W, Lin Shu-Min, Goodman Richard B, Mongovin Steve M, Wong Venus, Ballman Kim, Daubeuf Bruno, Elson Greg, Martin Thomas R
Pulmonary Research Laboratories at the Seattle Department of Veterans Affairs Medical Center, University of Washington School of Medicine, 151L 1660 South Columbian Way, Seattle, WA 98108, USA.
Gene. 2005 Jan 3;344:193-202. doi: 10.1016/j.gene.2004.09.032. Epub 2004 Nov 21.
Sepsis, a common sequela to Gram-negative pneumonia, results in considerable morbidity and mortality in hospitalized patients. The goal of this study was to determine whether Gram-negative pneumonia alters the expression TLR2, TLR4, and MD2 in lungs or in organs distant to the site of the primary infection. The cDNA sequence coding open reading frames for rabbit TLR2, TLR4, and MD2 were cloned and expressed in Escherichia coli, and specific polyclonal antibodies and polymerase chain reaction (PCR) probes were produced to identify changes in these receptors in rabbits with Gram-negative pneumonia. Using tissues from lungs and distant organs, we show that TLR2, TLR4, and MD2 gene expression is differentially regulated in rabbits with E. coli pneumonia. The increased expression of TLR2 and TLR4 could play an important role in the innate immune response to bacterial infection in the lungs, and improve pathogen recognition and bacterial clearance. In contrast, the increased gene expression of TLR2, TLR4, and MD2 in organs distant to the primary site of infection may contribute to the deleterious systemic inflammatory response observed in patients with sepsis.
脓毒症是革兰氏阴性菌肺炎常见的后遗症,可导致住院患者出现相当高的发病率和死亡率。本研究的目的是确定革兰氏阴性菌肺炎是否会改变肺部或原发性感染部位以外器官中Toll样受体2(TLR2)、Toll样受体4(TLR4)和髓系分化蛋白2(MD2)的表达。编码兔TLR2、TLR4和MD2开放阅读框的cDNA序列被克隆并在大肠杆菌中表达,同时制备了特异性多克隆抗体和聚合酶链反应(PCR)探针,以识别革兰氏阴性菌肺炎兔体内这些受体的变化。利用来自肺部和远处器官的组织,我们发现大肠杆菌肺炎兔体内TLR2、TLR4和MD2基因表达受到不同程度的调节。TLR2和TLR4表达的增加可能在肺部对细菌感染的固有免疫反应中发挥重要作用,并改善病原体识别和细菌清除。相比之下,原发性感染部位以外器官中TLR2、TLR4和MD2基因表达的增加可能导致脓毒症患者出现有害的全身炎症反应。