title: A prothrombin activator (Lopap) modulating inflammation, coagulation and cell survival mechanisms.
abstract: A severe hemorrhagic syndrome produced by contact with Lonomia obliqua caterpillars has become epidemic in southern Brazil. A significant thrombin production with intense consumption of fibrinogen and high D-dimer production indicates a consumption coagulopathy and secondary fibrinolysis in patients. Lopap is a single-chain 69kDa serine protease isolated from the crude extract of L. obliqua bristles. Experiments in mice showed that the purified protein, similar to the crude extract, causes uncoagulable blood by fibrinogen depletion. In order to characterize the effects of Lopap on cells involved with hemostatic system, we performed experiments using human umbilical vein endothelial cells (HUVECs). Our results show that Lopap exerts a direct effect on endothelial cells by increasing the liberation of molecules involved in the regulation of vascular tone, inhibiting platelet activation and chemotaxis, apart from inducing the expression of cell adhesion molecules which participate in inflammatory responses. The release or new synthesis of mediators involved in coagulation as von Willebrand factor and tissue factor, or in fibrinolysis as tissue plasminogen activator, was not affected by Lopap. Also our results demonstrated that Lopap acts on cell survival of HUVECs, regulating the expression of molecules as NO and avoiding cell death.
authors.affiliation: Biochemistry and Biophysics Laboratory, Butantan Institute, São Paulo, Brazil.
authors.forename: Márcio
authors.initials: M
authors.lastname: Fritzen
authors.forename: Miryam Paola Alvarez
authors.initials: MP
authors.lastname: Flores
authors.forename: Cleyson Valença
authors.initials: CV
authors.lastname: Reis
authors.forename: Ana Marisa
authors.initials: AM
authors.lastname: Chudzinski-Tavassi
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001777:Blood Coagulation / Q000187:drug effects* / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D007249:Inflammation / Q000276:immunology*; D011516:Prothrombin / Q000819:agonists*; D012697:Serine Endopeptidases / Q000008:administration & dosage*
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D007155:Immunologic Factors; D011516:Prothrombin; C119835:Lonomia obliqua prothrombin activator protease; D012697:Serine Endopeptidases