Lonomia obliqua venomous secretion induces human platelet adhesion and aggregation

Laboratório de Bioquímica Farmacológica, Centro de Biotecnologia UFRGS, Av Bento Gonçalves 9500, PO Box 15005, ZIP Code 91501-970 Porto Alegre, RS, Brazil.
Journal of Thrombosis and Thrombolysis (Impact Factor: 2.17). 02/2010; 30(3):300-10. DOI: 10.1007/s11239-010-0449-5
Source: PubMed


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.

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Available from: Carlos Termignoni, May 29, 2015
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    • "Several studies shown that Lonomia obliqua venom is able to induce pain, edema formation, erythema and fall of arterial pressure, probably due to the presence of several activities such as nociceptive and edematogenic (91), hyaluronidase (95) and kallikrein-kinin system activation activity (93). On the other hand, clinical and experimental studies suggest a combination of toxins which lead to systemic effects such as intravascular hemolysis, inflammation, platelet aggregation and adhesion dysfunction, consumption coagulopathy and incoagulability [37] [38] [39] [86] [87] [88] [89]. "
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    ABSTRACT: Lepidoptera species are widely distributed around the world and the majority of medically important envenoming occurs after the contact of human skin with the hairs or bristles of the larva form (caterpillars). In most occasions, the adverse effects are self-limited and the treatment is based on the use of antipruritics and oral antihistamines. However, envenomation caused by the South American Lonomia obliqua caterpillar (family: Saturniidae), can lead to a hemorrhagic syndrome characterized by coagulation disorders. A specific anti-serum had to be produced for an effective treatment against the caterpillar venom and for re-establishing the coagulation parameters in poisoned patients. The biological cycle of L. obliqua is composed by 4 phases with distinct durations (egg, larva with 6 instars, pupa, and adult). Human envenoming usually occurs with larvae between instars 4 to 6. After the contact with the human skin, caterpillar bristles are broken and the toxic principle quickly reaches the bloodstream, affecting mainly the hemostatic system. Recent studies have demonstrated that the mechanisms triggered by L. obliqua toxins are complex and some multifunctional toxins have been related to the pathophysiology of envenoming but also related to the development process of the animal, such as regulation of the cell cycle. The main toxins isolated from this venom (a prothrombin activator and a factor X activator) act at different levels on the coagulation cascade. This chapter reviews the information currently available about distribution, morphological aspects, adverse effects in humans and venomous components related to the Lonomia obliqua caterpillar that have been described so far.
    Lepidoptera: Classification, Behavior and Ecology, First edited by Elia Guerri, Johannes DeSare, 01/2013: chapter South American Lonomia obliqua Caterpillars: Morphological Aspects and Venom Biochemistry: pages 169-186; Nova Science Publishers Inc.., ISBN: 978-1-62417-248-9
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    • "This clear and typical inflammatory response occurred without the hemorrhage usually described for L. obliqua envenomation, although an intravascular effect on coagulation system cannot be discharge. For example, the potent pro-coagulant components of the venom may act triggering intravascular platelet aggregation and blood clotting (Berger et al., 2010), and then contribute to slow down blood flow, to the activation of endothelial vascular cells and the overall inflammatory panel. Increase in vascular permeability requires cytoskeleton reorganization, a necessary prerequisite to interendothelial cell gap formation. "
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    ABSTRACT: Lonomia obliqua envenomation is characterized by intense local inflammatory reaction, which, dependent on the severity of the case, is followed by severe clinical manifestations related to hemorrhagic disorders that can lead to fatal outcome. These effects were imputed to several toxins present in L. obliqua venom, which are responsible for procoagulant, anticoagulant as well as antithrombotic activities, being also able to interfere with vascular cells functions. In this work, the intravital microscopy analysis show that after administration of low doses of L. obliqua venom (1-3 μg/ml) on hamster cheek pouch, there was no alterations neither on arterioles or venules caliber nor in the vascular permeability up to 30 min. However, after 10 min in contact with venom occurred a clear activation in the vascular bed, characterized by an increase in leukocyte rolling and adhesion on endothelium of hamster cheek pouch venules. A confocal analysis of vascular beds, confirmed these results showing an increase in endothelial E-selectin and VCAM-1 expression. The effects of L. obliqua venom on human endothelial cell (EC) in vitro were also investigated. The treatment of EC with venom (1-3 μg/ml) did not affect cell viability. However, at concentrations as low as 3 μg/ml of L. obliqua venom modifies actin cytoskeleton dynamics, and increases focal adhesion contacts, inducing stress fiber formation, focal adhesion kinase (FAK) phosphorylation and its subsequent association to actin. These effects are followed by the activation of NF-κB pathway, a critical signaling in several events associated to vascular inflammation. Accordingly, L. obliqua venom leads to a significant increase in COX-2, NOS-2, HO-1, MMP-2 and MMP-9 expression. Taken together the data show that, even at low concentrations, L. obliqua venom can activate endothelial cells, which assume a pro-inflammatory profile, contributing for local effects and probably also for systemic disturbances due to its ability to modulate the properties of the vascular system.
    Toxicon 07/2012; 60(1):50-60. DOI:10.1016/j.toxicon.2012.03.016 · 2.49 Impact Factor
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    ABSTRACT: Despite the nearly worldwide distribution of Lepidoptera, there are few species with clear documentation of adverse reactions in humans. Most syndromes caused by Lepidoptera are consequences of direct contact with the hairs or setae of caterpillars. In most instances, the adverse effects caused by moth and caterpillars are self-limited and the treatment is based on the removal of hairs, application of topical antipruritics and, in some cases, the use of oral antihistamines. However, in the case of envenoming by South American Lonomiaobliqua caterpillars, the antilonomic serum produced at Instituto Butantan in Brazil is the only effective treatment to re-establish the physiological coagulation parameters in poisoned patients and to abolish the complications seen in severe cases (e.g. consumptive coagulopathy, intracerebral hemorrhage, and acute renal failure). Many studies have been carried out to understand the pathophysiological mechanism of envenoming by L. obliqua. Several toxic principles were found in bristle extract and the hemolymph, probably related to the envenoming. An interesting fact is that some toxins from the venom usually have more than one function. With the advent of molecular biology techniques it has become possible to analyze these processes at a molecular level, thus giving rise to hypotheses on the molecular basis of envenomation. This review contributes to enhance our understanding of the dramatic alterations that hemorrhagic syndrome causes in patients, current treatment, and the diversity of the molecules involved in this pathology.
    Pathophysiology of Haemostasis and Thrombosis 01/2010; 37(1):1-16. DOI:10.1159/000320067 · 2.24 Impact Factor
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