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1.
Toxins (Basel) ; 15(11)2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37999488

RESUMO

L-Amino acid oxidase (LAAO) is an enzyme found in snake venom that has multifaceted effects, including the generation of hydrogen peroxide (H2O2) during oxidative reactions, leading to various biological and pharmacological outcomes such as apoptosis, cytotoxicity, modulation of platelet aggregation, hemorrhage, and neutrophil activation. Human neutrophils respond to LAAO by enhancing chemotaxis, and phagocytosis, and releasing reactive oxygen species (ROS) and pro-inflammatory mediators. Exosomes cellular nanovesicles play vital roles in intercellular communication, including immune responses. This study investigates the impact of Calloselasma rhodostoma snake venom-derived LAAO (Cr-LAAO) on human neutrophil exosome release, including activation patterns, exosome formation, and content. Neutrophils isolated from healthy donors were stimulated with Cr-LAAO (100 µg/mL) for 3 h, followed by exosome isolation and analysis. Results show that Cr-LAAO induces the release of exosomes with distinct protein content compared to the negative control. Proteomic analysis reveals proteins related to the regulation of immune responses and blood coagulation. This study uncovers Cr-LAAO's ability to activate human neutrophils, leading to exosome release and facilitating intercellular communication, offering insights into potential therapeutic approaches for inflammatory and immunological disorders.


Assuntos
Exossomos , L-Aminoácido Oxidase , Humanos , L-Aminoácido Oxidase/farmacologia , L-Aminoácido Oxidase/metabolismo , Neutrófilos , Exossomos/metabolismo , Peróxido de Hidrogênio/farmacologia , Proteômica , Venenos de Serpentes
2.
Int Immunopharmacol ; 112: 109194, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36041255

RESUMO

Phospholipases A2 (PLA2s) are proteins found in snake venoms with hemolytic, anticoagulant, myotoxic, edematogenic, bactericidal and inflammatory actions. In Bothrops jararacussu snake venom were isolated a Lys49-PLA2 (BthTX-I) and an Asp49-PLA2 (BthTX-II) with myotoxic and inflammatory actions. Both PLA2s can activate the NLRP3 inflammasome, an intracytoplasmic platform that recognizes molecules released when tissue is damaged liberating IL-1ß that contributes to the inflammatory response observed in envenoming. The dynamic of action of BthTX-I and BthTX-II in both thioglycollate (TG)-elicited macrophages and C2C12 myoblasts and the involvement of EP1 and EP2 receptors, and PGE2 in NLRP3 inflammasome activation were evaluated. Both toxins induced PGE2 liberation and inflammasome components (NLRP3, Caspase-1, ASC, IL-1ß, and IL18), IL-6, P2X7, COX-1, COX-2, EP2 and EP4 gene expression in TG-elicited macrophages but not in C2C12 myoblasts. EP2 (PF04418948) and EP4 (GW627368X) inhibitors abolished this effect. Both PLA2s also induced NLRP3 inflammasome protein expression that was abolished with the inhibitors used. Immunofluorescence and IL-1ß assays confirmed the NLRP3 activation in TG-elicited macrophages with the participation of both EP2 and EP4 receptors confirming their involvement in this effect. All in all, BthTX-I and BthTX-II activate macrophages and induce the NLRP3 inflammasome complex activation with the participation of the PGE2 via COX pathway and EP2 and EP4, both PGE2 receptors, contributing to the local inflammatory effects observed in envenoming.


Assuntos
Bothrops , Venenos de Crotalídeos , Animais , Camundongos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ciclo-Oxigenase 2/genética , Tioglicolatos , Interleucina-18 , Interleucina-6 , Fosfolipases A2 , Venenos de Serpentes , Macrófagos , Caspase 1 , Dinoprostona , Anticoagulantes , Poliésteres
3.
Sci Rep ; 12(1): 4706, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35304541

RESUMO

Convulxin (CVX), a C-type lectin-like protein isolated from the venom of the snake species, Crotalus durissus terrificus, stimulates platelet aggregation by acting as a collagen receptor agonist for glycoprotein VI found in the platelets. The effect of CVX on platelets has been studied, but its effect on human peripheral blood mononuclear cells (PBMCs) remains unclear. Given the significance of PBMCs in inflammation, this study explored the effect of CVX on PBMCs, specifically regarding NLRP3 inflammasome activation by assessing cell viability, ability to induce cell proliferation, reactive oxygen species (ROS) and nitric oxide production, interleukin (IL)-2 and IL-10 secretion, NLRP3 complex activation, and the role of C-type lectin-like receptors (CTLRs) in these. CVX was not toxic to PBMCs at the investigated concentrations and did not increase PBMC growth or IL-2 release; however, CVX induced IL-10 release and ROS generation via monocyte activation. It also activated the NLRP3 complex, resulting in IL-1ß induction. Furthermore, the interaction between CVX and Dectin-2, a CTLR, induced IL-10 production. CVX interaction with CTLR has been demonstrated by laminarin therapy. Because of the involvement of residues near the Dectin-2 carbohydrate-recognition site, the generation of ROS resulted in inflammasome activation and IL-1ß secretion. Overall, this work helps elucidate the function of CVX in immune system cells.


Assuntos
Venenos de Crotalídeos , Crotalus , Animais , Venenos de Crotalídeos/química , Crotalus/metabolismo , Humanos , Inflamassomos , Interleucina-10 , Interleucina-1beta , Lectinas Tipo C/metabolismo , Leucócitos Mononucleares/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espécies Reativas de Oxigênio
4.
Toxicon ; 198: 171-175, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34029603

RESUMO

Photobiomodulation using light-emitting diode (LED) treatment has analgesic and anti-inflammatory effects which can be an effective therapeutic associated with serum therapy for local treatment of snakebites. Here we explored the effects of LED treatment on isolated macrophage under Bothrops jararacussu venom. Results showed that LED induced IL-6 and TNF-α genes down-regulation and, TGF and ARG1 genes up-regulation which indicates a polarization of macrophages to an M2 phenotype contributing to both tissue repair and resolution of inflammation.


Assuntos
Bothrops , Venenos de Crotalídeos , Terapia com Luz de Baixa Intensidade , Animais , Macrófagos , Camundongos , Fenótipo
5.
Chem Biol Interact ; 333: 109347, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33259806

RESUMO

Several reports have suggested that photobiomodulation, owing to its analgesic, anti-inflammatory, and healing effects, may be an effective therapeutic option for local effects of snakebites when the availability and accessibility of conventional serum therapy are inefficient and far from medical care centers. Although there have been studies that demonstrate the application of photobiomodulation in the treatment of local adverse events due to snakebites from snakes of the genus Bothrops, its role in the activation of leukocytes, particularly macrophages, has not been evaluated. Here, we assessed the effect of light-emitting diode (LED) treatment on macrophage activation induced by B. jararacussu venom (BjV). LED treatment caused an increase in the viability of macrophages incubated with BjV. This treatment reduced reactive oxygen species (ROS) and nitric oxide (NO) production by macrophages after incubation with BjV. However, LED treatment did not interfere with IL-1ß and IL-10 production by macrophages after incubation with BjV. In conclusion, this study showed that LED treatment has the potential to be used in combination with conventional serum therapy to prevent or minimize the progression of local to severe symptoms after Bothrops envenomation.


Assuntos
Bothrops , Venenos de Crotalídeos/toxicidade , Terapia com Luz de Baixa Intensidade/instrumentação , Macrófagos/efeitos da radiação , Semicondutores , Mordeduras de Serpentes/imunologia , Mordeduras de Serpentes/radioterapia , Animais , Sobrevivência Celular/efeitos dos fármacos , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espaço Intracelular/efeitos da radiação , Macrófagos/imunologia , Masculino , Camundongos , Óxido Nítrico/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Mordeduras de Serpentes/metabolismo , Mordeduras de Serpentes/patologia , Superóxidos/metabolismo
6.
Toxicon X ; 6: 100032, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32550587

RESUMO

Bothrops envenomation is associated with a cellular inflammatory response, characterized by pronounced neutrophil infiltration at the site of injury. Neutrophils act as the first line of defence, owing to their ability to migrate to the infected tissue, promoting an acute inflammatory response. At the site of inflammation, neutrophils perform defence functions such as phagocytosis, release of proteolytic enzymes, generation of reactive oxygen species (ROS), and synthesis of inflammatory mediators such as cytokines and lipid mediators. Neutrophils can also form neutrophil extracellular nets (NETs), webs composed of chromatin and granule proteins. This occurs after neutrophil activation and delivers high concentrations of anti-microbial molecules to the site of injury. This study evaluated the impact of BaTX-II, an Asp49 phospholipase A2 (PLA2) isolated from Bothrops atrox snake venom on human neutrophils in vitro. At non-toxic concentrations, BaTX-II induced hydrogen peroxide production by neutrophils, and this was reduced by wortmannin, a PI3K inhibitor. BaTX-II stimulated IL-1ß, IL-8, LTB4, myeloperoxidase (MPO), and DNA content release, consistent with NET formation. This is the first study to show the triggering of relevant pro-inflammatory events by PLA2 Asp49 isolated from secretory venom.

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