Kalayoglu M V, Byrne G I
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
Infect Immun. 1998 Nov;66(11):5067-72. doi: 10.1128/IAI.66.11.5067-5072.1998.
Chlamydia pneumoniae infection is associated with atherosclerotic heart and vessel disease, but a causal relationship between this pathogen and the disease process has not been established. Recently, it was reported that C. pneumoniae induces human macrophage foam cell formation, a key event in early atheroma development, suggesting a role for the organism in atherogenesis. This study further examines C. pneumoniae-induced foam cell formation in the murine macrophage cell line RAW-264.7. Infected RAW cells accumulated cholesteryl esters when cultured in the presence of low-density lipoprotein in a manner similar to that described for human macrophages. Exposure of C. pneumoniae elementary bodies to periodate, but not elevated temperatures, inhibited cholesteryl ester accumulation, suggesting a role for chlamydial lipopolysaccharide (cLPS) in macrophage foam cell formation. Purified cLPS was found to be sufficient to induce cholesteryl ester accumulation and foam cell formation. Furthermore, the LPS antagonist lipid X inhibited C. pneumoniae and cLPS-induced lipid uptake. These data indicate that cLPS is a C. pneumoniae component that induces macrophage foam cell formation and suggest that infected macrophages chronically exposed to cLPS may accumulate excess cholesterol to contribute to atheroma development.
肺炎衣原体感染与动脉粥样硬化性心脏和血管疾病相关，但这种病原体与疾病进程之间的因果关系尚未确立。最近，有报道称肺炎衣原体可诱导人巨噬细胞泡沫细胞形成，这是早期动脉粥样硬化发展中的关键事件，提示该病原体在动脉粥样硬化形成中发挥作用。本研究进一步检测了肺炎衣原体在小鼠巨噬细胞系RAW-264.7中诱导的泡沫细胞形成。当在低密度脂蛋白存在的情况下培养时，被感染的RAW细胞以类似于人巨噬细胞的方式积累胆固醇酯。将肺炎衣原体原体暴露于高碘酸盐而非升高的温度下，可抑制胆固醇酯积累，提示衣原体脂多糖（cLPS）在巨噬细胞泡沫细胞形成中发挥作用。发现纯化的cLPS足以诱导胆固醇酯积累和泡沫细胞形成。此外，LPS拮抗剂脂质X可抑制肺炎衣原体和cLPS诱导的脂质摄取。这些数据表明cLPS是肺炎衣原体的一种成分，可诱导巨噬细胞泡沫细胞形成，并提示长期暴露于cLPS的受感染巨噬细胞可能会积累过量胆固醇，从而促进动脉粥样硬化发展。
