Molestina R E, Dean D, Miller R D, Ramirez J A, Summersgill J T
Department of Medicine, University of Louisville School of Medicine, Kentucky 40292, USA.
Infect Immun. 1998 Apr;66(4):1370-6. doi: 10.1128/IAI.66.4.1370-1376.1998.
Chlamydia pneumoniae is a respiratory pathogen that has been associated with chronic inflammatory diseases such as asthma and atherosclerosis. Recent isolation of C. pneumoniae from human carotid and coronary atheromas provides additional support for a role of this organism in atherogenesis. We characterized the coronary strain C. pneumoniae A-03 by sequence analysis of the major outer membrane protein gene (omp1). In addition, the in vitro activities of A-03 and three respiratory strains of C. pneumoniae (BAL-16, TW-183, and T-2634) were examined in infected human umbilical vein endothelial cells (HUVEC) by analysis of the production of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and soluble intercellular cell adhesion molecule 1 (sICAM-1). Sequence analysis of omp1 of C. pneumoniae A-03, compared to prototype strains TW-183 and AR-39, revealed five nucleotide changes resulting in nonsynonymous codons. Of interest was a nonconservative amino acid substitution (Ser to Pro) in position 61 of variable segment 1. In vitro, the extent of MCP-1, IL-8, and sICAM-1 production was dependent on the C. pneumoniae strain examined at low multiplicities of infection following 24 h of incubation. Strain A-03 displayed the lowest stimulatory activity in infected HUVEC, while T-2634 induced the highest levels of MCP-1, IL-8, and sICAM-1 among all strains examined. Heat-inactivated C. pneumoniae failed to stimulate production of these proteins by all strains tested. In contrast, only partial inhibition was observed by UV-inactivated organisms. Results from this study demonstrate that unlike prototype respiratory strains of C. pneumoniae, the coronary strain A-03 displays divergence in the omp1 gene. In addition, the stimulation of chemokines and adhesion molecules involved in the recruitment of leukocytes to sites of inflammation by C. pneumoniae may be important in the pathogenesis of diseases associated with this organism, including atherosclerosis.
肺炎衣原体是一种呼吸道病原体，与哮喘和动脉粥样硬化等慢性炎症性疾病有关。最近从人类颈动脉和冠状动脉粥样斑块中分离出肺炎衣原体，为该生物体在动脉粥样硬化发生中的作用提供了更多支持。我们通过对主要外膜蛋白基因（omp1）进行序列分析，对冠状动脉菌株肺炎衣原体A-03进行了表征。此外，通过分析白细胞介素-8（IL-8）、单核细胞趋化蛋白1（MCP-1）和可溶性细胞间黏附分子1（sICAM-1）的产生，在感染的人脐静脉内皮细胞（HUVEC）中检测了A-03和三种肺炎衣原体呼吸道菌株（BAL-16、TW-183和T-2634）的体外活性。与原型菌株TW-183和AR-39相比，肺炎衣原体A-03的omp1序列分析揭示了五个导致非同义密码子的核苷酸变化。有趣的是，可变区1第61位发生了非保守氨基酸取代（丝氨酸变为脯氨酸）。在体外，孵育24小时后，在低感染复数下，MCP-1、IL-8和sICAM-1的产生程度取决于所检测的肺炎衣原体菌株。菌株A-03在感染的HUVEC中显示出最低的刺激活性，而T-2634在所有检测菌株中诱导产生的MCP-1、IL-8和sICAM-1水平最高。热灭活的肺炎衣原体不能刺激所有测试菌株产生这些蛋白质。相比之下，紫外线灭活的生物体仅观察到部分抑制作用。这项研究的结果表明，与肺炎衣原体的原型呼吸道菌株不同，冠状动脉菌株A-03在omp1基因上存在差异。此外，肺炎衣原体对参与白细胞募集到炎症部位的趋化因子和黏附分子的刺激，在与该生物体相关的疾病（包括动脉粥样硬化）的发病机制中可能很重要。
