Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression.
نویسندگان
چکیده
Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coagulation in infected vessels. Whereas uninfected endothelial cell cultures showed essentially undetectable TF mRNA and activity, both TF mRNA and activity were present after R rickettsii infection. TF mRNA levels were transient, peaking at 4 hours after the initiation of infection, whereas the peak of TF activity occurred at 8 hours. Induction of the TF response requires the intracellular presence of R rickettsii organisms, because uninfected rickettsia were ineffective and the response was blocked by inhibiting rickettsial entry using cytochalasin B. TF induction was not mediated by endothelial cell release of soluble factor, because no response was induced using culture medium conditioned by R rickettsii-infected cells. Furthermore, preadsorption of suspensions of R rickettsii with polymyxin B to remove contaminating lipopolysaccharide did not eliminate the TF response. Induction of TF in vital endothelial cells during R rickettsii infection could be the trigger for vascular thrombus formation of RMSF.
منابع مشابه
Rickettsia rickettsii Infection of Cultured Human Endothelial Cells Induces Tissue Factor Expression
Microvascular thrombi underlie many of the clinical manifestations of Rocky Mountain spotted fever (RMSF), a disease characterized by Rickettsia rickettsii infection of vascular endothelial cells. Studies were designed to determine whether R rickettsii-infection of cultured human umbilical vein endothelial cells results in tissue factor (TF) induction, a process that could directly activate coa...
متن کاملTissue factor mRNA expression in the endothelium of an intact umbilical vein.
Tissue factor (TF) mRNA expression was measured by in situ hybridization in the endothelium of the intact human umbilical vein after infection with Rickettsia rickettsii. At 4 hours, R rickettsii organisms were clearly visible within approximately 70% of endothelial cells by immunocytochemical staining. Quantitation of TF mRNA expression revealed that the level within endothelial cells of the i...
متن کاملRickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies.
The clinical manifestations of Rocky Mountain spotted fever (RMSF) result from Rickettsia rickettsii (R rickettsii) infection of endothelial cells and are mediated by pathologic changes localized to the vessel, including in situ thrombosis and tissue ischemia. This study uses in vitro infection of cultured human umbilical vein endothelial cells with R rickettsii to test the hypothesis that such...
متن کاملRickettsia rickettsii Infection of Cultured Human Endothelial Cells Induces NF-kB Activation
متن کامل
Involvement of protein kinase C in Rickettsia rickettsii-induced transcriptional activation of the host endothelial cell.
Our laboratory has reported on a biphasic pattern of nuclear factor kappaB (NF-kappaB) activation in cultured human umbilical vein endothelial cells during infection with Rickettsia rickettsii, an obligate, intracellular bacterium, and the etiologic agent of Rocky Mountain spotted fever. Transcriptional activation of the tissue factor (TF) gene during this infection has been shown to involve NF...
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ورودعنوان ژورنال:
- Blood
دوره 83 6 شماره
صفحات -
تاریخ انتشار 1994