title: Vascular endothelial cell injury induced by Bothrops jararaca venom; non-significance of hemorrhagic metalloproteinase.
abstract: To examine the effect of Bothrops jararaca venom and its major hemorrhagic metalloproteinase, jararafibrase I (JF I), on vascular endothelial cells, B. jararaca crude venom and JF I were infused intravenously into rabbits. The degree of endothelial cell injury was estimated from the plasma level of soluble thrombomodulin (TM). The fibrinogen level, prothrombin time (PT), JF I antigen level and macroglobulin activity of the plasma were also measured. The TM level was not increased even by a large quantity of JF I, while the crude venom caused an increase in TM level suggesting the occurrence of endothelial cell injury. No alterations of fibrinogen level and PT were noted with a high amount of JF I, and no systemic bleeding was observed. Macroglobulin, which is the main inhibitor of metalloproteinase in rabbit plasma, was not significantly reduced despite a high dose of JF I. The elevation of TM level in the rabbit plasma after infusion of crude venom was totally suppressed by pretreatment with heparin. These findings suggest that the endothelial cell injury caused by B. jararaca venom is not due to the hemorrhagic metalloproteinase but to the coagulating factors in the venom. Plasma macroglobulin appears to be efficient enough to neutralize the circulating hemorrhagic metalloproteinases inoculated by B. jararaca.
authors.affiliation: Department of Physiology, Miyazaki Medical College, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Kawano
authors.forename: Keita
authors.initials: K
authors.lastname: Anai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugiki
authors.forename: Etsuo
authors.initials: E
authors.lastname: Yoshida
authors.forename: Masugi
authors.initials: M
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D000941:Antigens / Q000097:blood; D017837:Bothrops; D002478:Cells, Cultured / Q000187:drug effects; D003435:Crotalid Venoms / Q000008:administration & dosage / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005340:Fibrinogen / Q000378:metabolism; D006470:Hemorrhage / Q000139:chemically induced; D008259:Macroglobulins / Q000378:metabolism; D008297:Male; D008666:Metalloendopeptidases / Q000276:immunology / Q000633:toxicity*; D011517:Prothrombin Time; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D018180:Thrombomodulin / Q000097:blood
chemical_list: D000941:Antigens; D003435:Crotalid Venoms; D008259:Macroglobulins; D018180:Thrombomodulin; D005340:Fibrinogen; D008666:Metalloendopeptidases; C076581:jararafibrase I