Reife R A, Shapiro R A, Bamber B A, Berry K K, Mick G E, Darveau R P
Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington 98121, USA.
Infect Immun. 1995 Dec;63(12):4686-94. doi: 10.1128/iai.63.12.4686-4694.1995.
Porphyromonas gingivalis is a gram-negative bacterium that is associated with periodontitis. It has been hypothesized that destruction of bone and periodontal connective tissue is associated with colonization of the subgingival crevicular space by P. gingivalis, although how these bacteria overcome innate host defenses is largely unknown. To examine the early cellular and molecular events of P. gingivalis interaction with host tissues, we compared lipopolysaccharide (LPS) isolated from this bacterium with Escherichia coli LPS, a potent inflammatory mediator, in a mouse model of acute inflammation. In these studies, mice were given intramuscular injections of either P. gingivalis LPS or E. coli LPS and then sacrificed after 4 h. Reverse transcriptase-PCR analysis showed that expression of mRNAs for E- and P-selectins was higher in E. coli LPS-injected muscles than in P. gingivalis LPS-injected or control phosphate-buffered-saline-injected muscles. Similarly, monocyte chemotactic protein 1 and fibroblast-induced cytokine mRNAs were expressed in E. coli LPS-injected muscles whereas their expression was reduced or absent in P. gingivalis LPS-injected samples. These results were confirmed by in situ hybridization whereby stronger hybridization for selectin mRNAs was observed in the endothelium of capillaries from E. coli LPS-injected samples than in that from P. gingivalis LPS-injected muscles. In addition, many monocytes expressing monocyte chemotactic protein 1 mRNA and polymorphonuclear leukocytes expressing fibroblast-induced cytokine mRNA were observed in E. coli LPS-injected muscles whereas only a few cells were identified in P. gingivalis LPS-injected muscles. These results demonstrate that compared with E. coli, P. gingivalis has a low biologically reactive LPS as measured by its weak activation of inflammation. This may allow P. gingivalis to evade innate host defense mechanisms, resulting in colonization and chronic disease.
牙龈卟啉单胞菌是一种与牙周炎相关的革兰氏阴性菌。据推测,骨组织和牙周结缔组织的破坏与牙龈卟啉单胞菌在龈下沟间隙的定植有关,尽管这些细菌如何克服宿主的固有防御机制在很大程度上尚不清楚。为了研究牙龈卟啉单胞菌与宿主组织相互作用的早期细胞和分子事件,我们在急性炎症小鼠模型中,将从该细菌分离的脂多糖(LPS)与一种强效炎症介质大肠杆菌LPS进行了比较。在这些研究中,给小鼠肌肉注射牙龈卟啉单胞菌LPS或大肠杆菌LPS,4小时后处死。逆转录酶 - PCR分析表明,注射大肠杆菌LPS的肌肉中E选择素和P选择素的mRNA表达高于注射牙龈卟啉单胞菌LPS或对照磷酸盐缓冲盐水的肌肉。同样,单核细胞趋化蛋白1和成纤维细胞诱导细胞因子的mRNA在注射大肠杆菌LPS的肌肉中表达,而在注射牙龈卟啉单胞菌LPS的样本中其表达减少或缺失。这些结果通过原位杂交得到证实,即观察到注射大肠杆菌LPS样本的毛细血管内皮中选择素mRNA的杂交比注射牙龈卟啉单胞菌LPS肌肉中的更强。此外,在注射大肠杆菌LPS的肌肉中观察到许多表达单核细胞趋化蛋白1 mRNA的单核细胞和表达成纤维细胞诱导细胞因子mRNA的多形核白细胞,而在注射牙龈卟啉单胞菌LPS的肌肉中仅鉴定出少数细胞。这些结果表明,与大肠杆菌相比,牙龈卟啉单胞菌的LPS具有低生物反应性,这通过其对炎症的弱激活来衡量。这可能使牙龈卟啉单胞菌逃避宿主的固有防御机制,从而导致定植和慢性疾病。