Rickettsial phospholipase A2 as a pathogenic mechanism in a model of cell injury by typhus and spotted fever group rickettsiae.
Phospholipase A2 activity by typhus group rickettsiae causes hemolysis in vitro. Rickettsial phospholipase A2 has been proposed to mediate entry into the host cell, escape from the phagosome, and cause injury to host cells by both typhus and spotted fever group rickettsiae. In a rickettsial contact-associated cytotoxicity model, the interaction of Rickettsia prowazekii or R. conorii with Vero cells caused temperature-dependent release of 51Cr from the cells. Treatment of rickettsiae, but not the cells, with a phospholipase A2 inhibitor (bromophenacyl bromide) or with antibody to king cobra venom inhibited cell injury. Rickettsial treatment with bromophenacyl bromide inhibited the release of free fatty acids from the host cell. Neither the inhibitor nor antivenom impaired rickettsial active transport of L-lysine. Thus, host cell injury was mediated by a rickettsial phospholipase A2-dependent mechanism.
Walker
D H
DH
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA.
Feng
H M
HM
Popov
V L
VL
D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000906:Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D000997:Antivenins / Q000494:pharmacology / Q000627:therapeutic use; D001907:Boutonneuse Fever / Q000188:drug therapy; D002522:Chlorocebus aethiops; D003601:Cytotoxicity Tests, Immunologic; D004546:Elapid Venoms / Q000201:enzymology / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008954:Models, Biological; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000276:immunology*; D054467:Phospholipases A2; D020114:Rickettsia conorii / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity*; D012283:Rickettsia prowazekii / Q000187:drug effects / Q000201:enzymology / Q000472:pathogenicity*; D014438:Typhus, Epidemic Louse-Borne / Q000188:drug therapy; D014709:Vero Cells / Q000187:drug effects / Q000382:microbiology / Q000648:ultrastructure*
D000098:Acetophenones; D000906:Antibodies; D000997:Antivenins; D004546:Elapid Venoms; D004791:Enzyme Inhibitors; D010741:Phospholipases A; D054467:Phospholipases A2; C006821:4-bromophenacyl bromide