Rickettsia rickettsii-induced cellular injury of human vascular endothelium in vitro

The endothelial cell is the putative primary target cell in humans infected with Rickettsia rickettsii, the etiological agent of Rocky Mountain spotted fever. Although the clinical manifestations of infection by this organism are well documented, the mechanism of injury to the endothelial cell is not understood. The ability to culture human endothelial cells in vitro provides a unique system with which to study this host-parasite interaction directly. Human vascular endothelial cells derived from the umbilical vein, when infected by R. rickettsii, became severely damaged within a few days postinfection. The primary lesion observed at the ultrastructural level appeared to occur at intracellular membranes, specifically, the rough-surfaced endoplasmic reticulum. Widespread dilatation of these membranes eventually led to the creation of large intracellular cisternae and the apparent circumscription of rickettsiae and cellular organelles by the rough-surfaced endoplasmic reticulum. Small membrane-bound fragments of host cytosol created by dilating membranes also were present within the cisternae. Within 5 to 6 days postinfection, cells lost their osmoregulatory control and lysed. Some possible mechanisms of cell injury directed at the level of intracellular membranes are discussed.