Loxosceles gaucho spider venom and its sphingomyelinase fraction trigger the main functions of human and rabbit platelets.
Loxosceles venoms can promote severe local and systemic damages. We have previously reported that Loxosceles gaucho spider venom causes a severe early thrombocytopenia in rabbits. Herein, we investigated the in vitro effects of this venom and its sphingomyelinase fraction on the main functions of platelets. Whole venom and its fraction induced aggregation of both human and rabbit platelets. Aggregation was dependent of plasma component(s) but independent of venom-induced lysophosphatidic acid generation. There was no increase in the levels of lactate dehydrogenase during platelet aggregation, ruling out the possibility of platelet lysis. The increased expression of ligand-induced binding site 1 (LIBS1) induced by L. gaucho venom and its sphingomyelinase fraction, as well as of P-selectin by the whole venom, evidenced the activation state of both human and rabbit platelets. Adhesion assays showed an irregular response when platelets were exposed to the whole venom, whereas the sphingomyelinase fraction induced a dose-dependent increase in the platelet adhesion to collagen. These findings evidence that L. gaucho venom and its sphingomyelinase fraction trigger adhesion, activation, and aggregation of both human and rabbit platelets. Thus, this work justifies the use of rabbits to investigate Loxosceles venom-induced platelet disturbances, and it also supports research on the role of platelets in the pathogenesis of loxoscelism.
Laboratório de Fisiopatologia, Instituto Butantan, São Paulo-SP, Brazil. flutavares@gmail.com
Flávio L
FL
Tavares
María E
ME
Peichoto
Danieli de Morais
Dde M
Rangel
Kátia C
KC
Barbaro
Maria Cristina
MC
Cirillo
Marcelo L
ML
Santoro
Ida S
IS
Sano-Martins
D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D039661:Integrin beta3 / Q000097:blood; D023421:Models, Animal; D019007:P-Selectin / Q000097:blood; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood; D011817:Rabbits / Q000097:blood*; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology*; D013111:Spider Venoms / Q000494:pharmacology*
D039661:Integrin beta3; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D040201:Platelet Membrane Glycoprotein IIb; D013111:Spider Venoms; C055161:loxosceles venom; D010727:Phosphoric Diester Hydrolases; D013108:Sphingomyelin Phosphodiesterase