Role of the inflammatory response in the hemorrhagic syndrome induced by the hemolymph of the caterpillar Lonomia achelous

Contact with the caterpillar of Lonomia achelous causes a hemorrhagic syndrome in humans prompted by two processes, an initial mild DIC that is later masked by overwhelming fibrinolytic activity. Although the venom affects both the hemostatic and inflammatory systems separately, it is not clear whet...

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Veröffentlicht in:Toxicon (Oxford) 2016-10, Vol.121, p.77-85
Hauptverfasser: Taylor, Peter, Salazar, Emelyn, Barrios, Mariana, Salazar, Ana María, Abad, María-Jesús, Urdanibia, Izaskun, Shealy, David, Arocha-Piñango, Carmen Luisa, Guerrero, Belsy
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container_issue
container_start_page 77
container_title Toxicon (Oxford)
container_volume 121
creator Taylor, Peter
Salazar, Emelyn
Barrios, Mariana
Salazar, Ana María
Abad, María-Jesús
Urdanibia, Izaskun
Shealy, David
Arocha-Piñango, Carmen Luisa
Guerrero, Belsy
description Contact with the caterpillar of Lonomia achelous causes a hemorrhagic syndrome in humans prompted by two processes, an initial mild DIC that is later masked by overwhelming fibrinolytic activity. Although the venom affects both the hemostatic and inflammatory systems separately, it is not clear whether the hematological and hemostatic disturbances may in part be due to an indirect effect via inflammatory mediators. Here we report results on the crosstalk between these systems, particularly the effect of the pro-inflammatory cytokine TNF-α on hemostatic parameters. Materials and Methods: the nitric oxide and TNF-α responses, as well as activation of the coagulation and fibrinolytic systems, were measured in macrophages and endothelial cells treated with Lonomia achelous hemolymph (LAH). The same responses were then determined, in a mouse model of LAH envenomation, after treatment with an anti-TNF-α antibody. Results: Both macrophages and endothelial cells responded strongly to LAH in terms of pro-inflammatory mediator release and fibrinolytic activities as well as pro-coagulant activity (TF activity) in endothelial cells. Treatment with antibody against TNF-α decreased both TNF-α and NO3−/NO2− serum levels in the mice, after LAH injection. Blocking TNF-α also modified significantly the serum levels of plasminogen, fibrinogen and FXIII in mice, as well as decreased TF activity in endothelial cells. Conclusions: LAH may induce a hemostatic effect through endothelial and macrophage activation. These activated cell release hemostatic enzymes as well as pro-inflammatory mediators, principally TNF-α, that potentiate this release in an autocrine fashion, amplifying the fibrinolytic effect, which may in turn exacerbate the hemorrhagic manifestations. As far as we are aware, this is the first report of the relationship between the hemostatic system and the inflammatory responses in a hemorrhagic syndrome induce by animal secretions. •Lonomia achelous hemolymph (LAH) causes a hemorrhagic syndrome in humans.•LAH stimulates strongly the hemostatic system as well as the innate immune system.•Lonomia achelous hemolymph might induce the fibrinolytic and pro-coagulant effect through macrophages and endothelial cells activation.•TNF-α release besides LAH may increase the inflammatory response causing a pro-fibrinolytic effect that lead to hemorrhage.•This is the first report describing the relationship between hemostasis and inflammation in the syndrome produced by LAH.
doi_str_mv 10.1016/j.toxicon.2016.08.018
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Although the venom affects both the hemostatic and inflammatory systems separately, it is not clear whether the hematological and hemostatic disturbances may in part be due to an indirect effect via inflammatory mediators. Here we report results on the crosstalk between these systems, particularly the effect of the pro-inflammatory cytokine TNF-α on hemostatic parameters. Materials and Methods: the nitric oxide and TNF-α responses, as well as activation of the coagulation and fibrinolytic systems, were measured in macrophages and endothelial cells treated with Lonomia achelous hemolymph (LAH). The same responses were then determined, in a mouse model of LAH envenomation, after treatment with an anti-TNF-α antibody. Results: Both macrophages and endothelial cells responded strongly to LAH in terms of pro-inflammatory mediator release and fibrinolytic activities as well as pro-coagulant activity (TF activity) in endothelial cells. Treatment with antibody against TNF-α decreased both TNF-α and NO3−/NO2− serum levels in the mice, after LAH injection. Blocking TNF-α also modified significantly the serum levels of plasminogen, fibrinogen and FXIII in mice, as well as decreased TF activity in endothelial cells. Conclusions: LAH may induce a hemostatic effect through endothelial and macrophage activation. These activated cell release hemostatic enzymes as well as pro-inflammatory mediators, principally TNF-α, that potentiate this release in an autocrine fashion, amplifying the fibrinolytic effect, which may in turn exacerbate the hemorrhagic manifestations. 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Treatment with antibody against TNF-α decreased both TNF-α and NO3−/NO2− serum levels in the mice, after LAH injection. Blocking TNF-α also modified significantly the serum levels of plasminogen, fibrinogen and FXIII in mice, as well as decreased TF activity in endothelial cells. Conclusions: LAH may induce a hemostatic effect through endothelial and macrophage activation. These activated cell release hemostatic enzymes as well as pro-inflammatory mediators, principally TNF-α, that potentiate this release in an autocrine fashion, amplifying the fibrinolytic effect, which may in turn exacerbate the hemorrhagic manifestations. 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Although the venom affects both the hemostatic and inflammatory systems separately, it is not clear whether the hematological and hemostatic disturbances may in part be due to an indirect effect via inflammatory mediators. Here we report results on the crosstalk between these systems, particularly the effect of the pro-inflammatory cytokine TNF-α on hemostatic parameters. Materials and Methods: the nitric oxide and TNF-α responses, as well as activation of the coagulation and fibrinolytic systems, were measured in macrophages and endothelial cells treated with Lonomia achelous hemolymph (LAH). The same responses were then determined, in a mouse model of LAH envenomation, after treatment with an anti-TNF-α antibody. Results: Both macrophages and endothelial cells responded strongly to LAH in terms of pro-inflammatory mediator release and fibrinolytic activities as well as pro-coagulant activity (TF activity) in endothelial cells. Treatment with antibody against TNF-α decreased both TNF-α and NO3−/NO2− serum levels in the mice, after LAH injection. Blocking TNF-α also modified significantly the serum levels of plasminogen, fibrinogen and FXIII in mice, as well as decreased TF activity in endothelial cells. Conclusions: LAH may induce a hemostatic effect through endothelial and macrophage activation. These activated cell release hemostatic enzymes as well as pro-inflammatory mediators, principally TNF-α, that potentiate this release in an autocrine fashion, amplifying the fibrinolytic effect, which may in turn exacerbate the hemorrhagic manifestations. As far as we are aware, this is the first report of the relationship between the hemostatic system and the inflammatory responses in a hemorrhagic syndrome induce by animal secretions. •Lonomia achelous hemolymph (LAH) causes a hemorrhagic syndrome in humans.•LAH stimulates strongly the hemostatic system as well as the innate immune system.•Lonomia achelous hemolymph might induce the fibrinolytic and pro-coagulant effect through macrophages and endothelial cells activation.•TNF-α release besides LAH may increase the inflammatory response causing a pro-fibrinolytic effect that lead to hemorrhage.•This is the first report describing the relationship between hemostasis and inflammation in the syndrome produced by LAH.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27576063</pmid><doi>10.1016/j.toxicon.2016.08.018</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-2755-1198</orcidid></addata></record>
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subjects Activation
Animals
Antibodies
Caterpillars
Disorders
Endothelial cells
Hemolymph - metabolism
Hemorrhage - etiology
Hemorrhagic syndrome
hemostasis
Hemostatics
Inflammation
Inflammation - etiology
Lonomia achelous
Macrophages
Male
Mice
Mice, Inbred C57BL
Moths
Nitric oxide
TNF
Tumor Necrosis Factor-alpha - metabolism
title Role of the inflammatory response in the hemorrhagic syndrome induced by the hemolymph of the caterpillar Lonomia achelous
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