Lonomia obliqua venomous secretion induces human platelet adhesion and aggregation.
The caterpillar Lonomia obliqua is a venomous animal that causes numerous accidents, especially in southern Brazil, where it is considered a public health problem. The clinical manifestations include several haemostatic disturbances that lead to a hemorrhagic syndrome. Considering that platelets play a central role in hemostasis, in this work we investigate the effects of L. obliqua venomous secretion upon blood platelets responses in vitro. Results obtained shows that L. obliqua venom directly induces aggregation and ATP secretion in human washed platelets in a dose-dependent manner. Electron microscopy studies clearly showed that the venomous bristle extract was also able to produce direct platelets shape change and adhesion as well as activation and formation of platelet aggregates. Differently from other enzyme inhibitors, the venom-induced platelet aggregation was significatively inhibited by p-bromophenacyl bromide, a specific inhibitor of phospholipases A2. Additional experiments with different pharmacological antagonists indicate that the aggregation response triggered by the venom active components occurs through a calcium-dependent mechanism involving arachidonic acid metabolite(s) of the cyclooxygenase pathway and activation of phosphodiesterase 3A, an enzyme that leads to the consumption of intracellular cAMP content. It was additionally found that L. obliqua-induced platelet aggregation was independent of ADP release. Altogether, these findings are in line with the need for a better understanding of the complex hemorrhagic syndrome resulting from the envenomation caused by L. obliqua caterpillars, and can also give new insights into the management of its clinical profile.
Laboratório de Bioquímica Farmacológica, Centro de Biotecnologia UFRGS, Av Bento Gonçalves 9500, PO Box 15005, ZIP Code 91501-970 Porto Alegre, RS, Brazil.
Markus
M
Berger
José
J
Reck
Renata M S
RM
Terra
Walter O
WO
Beys da Silva
Lucélia
L
Santi
Antônio F M
AF
Pinto
Marilene H
MH
Vainstein
Carlos
C
Termignoni
Jorge A
JA
Guimarães
D000098:Acetophenones / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism; D006470:Hemorrhage; D006801:Humans; D064801:Phospholipase A2 Inhibitors; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012697:Serine Endopeptidases / Q000494:pharmacology*
D000098:Acetophenones; D064801:Phospholipase A2 Inhibitors; D000255:Adenosine Triphosphate; D011451:Prostaglandin-Endoperoxide Synthases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C119835:Lonomia obliqua prothrombin activator protease; D012697:Serine Endopeptidases; C006821:4-bromophenacyl bromide