BACKGROUND: Chlamydia pneumoniae infections have been linked with myocardial infarction, stroke, and the development of atherosclerosis by epidemiologic studies, immunohistochemical studies, and electron microscopic studies. The mechanisms underlying this association are unknown. METHODS: Using cultured human venous endothelial cells, we investigated whether C pneumoniae, C trachomatis (types H and L2/434/BU) could infect these cells. The ability of infected cells to express procoagulant (tissue factor) activity was also measured using clotting and chromogenic substrate assays. Adhesion of platelets to chlamydia-infected cells was also quantitated. RESULTS: We found that C pneumoniae, C trachomatis type H, and C trachomatis L2/434/BU could infect cultured human umbilical vein endothelial cells and stimulate a 4-fold increase in expression of tissue factor, which reached a peak 18 hours postinfection. Tissue factor expression was enhanced even in the presence of tetracycline, suggesting that the chlamydial factor responsible for stimulating synthesis of endothelial cell tissue factor was preformed. Platelet adhesion was significantly enhanced when endothelial cells were infected by chlamydia species. CONCLUSIONS: These in vitro studies suggest possible pathogenic mechanisms that may explain the association of thrombotic events with C pneumoniae infection, including pathologically enhanced production of tissue factor by human endothelial cells and enhanced focal platelet deposition.
BACKGROUND:Chlamydia pneumoniae infections have been linked with myocardial infarction, stroke, and the development of atherosclerosis by epidemiologic studies, immunohistochemical studies, and electron microscopic studies. The mechanisms underlying this association are unknown. METHODS: Using cultured human venous endothelial cells, we investigated whether C pneumoniae, C trachomatis (types H and L2/434/BU) could infect these cells. The ability of infected cells to express procoagulant (tissue factor) activity was also measured using clotting and chromogenic substrate assays. Adhesion of platelets to chlamydia-infected cells was also quantitated. RESULTS: We found that C pneumoniae, C trachomatis type H, and C trachomatis L2/434/BU could infect cultured human umbilical vein endothelial cells and stimulate a 4-fold increase in expression of tissue factor, which reached a peak 18 hours postinfection. Tissue factor expression was enhanced even in the presence of tetracycline, suggesting that the chlamydial factor responsible for stimulating synthesis of endothelial cell tissue factor was preformed. Platelet adhesion was significantly enhanced when endothelial cells were infected by chlamydia species. CONCLUSIONS: These in vitro studies suggest possible pathogenic mechanisms that may explain the association of thrombotic events with C pneumoniae infection, including pathologically enhanced production of tissue factor by human endothelial cells and enhanced focal platelet deposition.