Heparin protects human endothelial cells infected by Rickettsia rickettsii.
Routine culture of endothelial cells currently includes the use of heparin, which significantly reduces cell doubling time and increases cell population size. Heparin protects cultured arterial endothelial cells from damage by toxic oxygen metabolites produced by the action of xanthine and xanthine oxidase. Because of our hypothesis implicating free radicals in cell injury caused by Rickettsia rickettsii, we have carried out a series of experiments to examine the effects of heparin on injury to endothelial cells infected by this microorganism. These studies showed that heparin does not inhibit replication of R. rickettsii in the cytoplasm of endothelial cells. Furthermore, heparin appears to exhibit a protective effect on the infected host cell as measured by (i) reduced plaque size, (ii) increased longevity of the cell monolayer, (iii) reduction in the amount of lactic dehydrogenase released from infected cells, and (iv) reduction in the levels of intracellular peroxides formed in infected cells. Electron microscopic studies also show a significant reduction in dilatation of the rough-surfaced endoplasmic reticulum of the infected cells in the presence of heparin. These observations appear to lend additional support to involvement of an oxidative mechanism in human endothelial cell injury caused by R. rickettsii.
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore 21201.
D J
DJ
Silverman
L A
LA
Santucci
Z
Z
Sekeyova
D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008854:Microscopy, Electron; D010084:Oxidation-Reduction; D010545:Peroxides / Q000032:analysis; D012284:Rickettsia rickettsii / Q000254:growth & development* / Q000472:pathogenicity
D000975:Antioxidants; D010545:Peroxides; D006493:Heparin