Bothrops snake venoms and their isolated toxins, an L-amino acid oxidase and a serine protease, modulate human complement system pathways

Ayres, Lorena Rocha; Récio, Alex dos Reis; Burin, Sandra Mara; Pereira, Juliana da Silva; Martins, Andrea Casella; Sampaio, Suely Vilela; Castro, Fabíola Attié de; Pereira-Crott, Luciana S.

doi:10.1186/s40409-015-0026-7

Cited by 22 publications

(12 citation statements)

References 37 publications

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“…This B. pirajai venom P-I class SVMP was also purified by another group (10), and it was shown to exert local inflammatory effects in vivo (11), which might be related to its anticomplementary activity. Other toxins from the venom of B. pirajai have also been implicated in the activation of the complement system, as demonstrated for two serine proteinases (12) and one LAO (13), although their effects on the complement system have been considered weak by the authors.…”

Section: Introductionmentioning

confidence: 99%

Complement System Inhibition Modulates the Pro-Inflammatory Effects of a Snake Venom Metalloproteinase

et al. 2019

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Envenomation by Bothrops snakes causes prominent local effects, including pain, oedema, local bleeding, blistering and necrosis, and systemic manifestations, such as hemorrhage, hypotension, shock and acute renal failure. These snake venoms are able to activate the complement system and induce the generation of anaphylatoxins, whose mechanisms include the direct cleavage of complement components by snake venom metalloproteinases and serine proteinases present in the venoms. A metalloproteinase able to activate the three complement pathways and generate active anaphylatoxins, named C-SVMP, was purified from the venom of Bothrops pirajai . Considering the inflammatory nature of Bothrops venoms and the complement-activation property of C-SVMP, in the present work, we investigated the inflammatory effects of C-SVMP in a human whole blood model. The role of the complement system in the inflammatory process and its modulation by the use of compstatin were also investigated. C-SVMP was able to activate the complement system in the whole blood model, generating C3a/C3a desArg, C5a/C5a desArg and SC5b-9. This protein was able to promote an increase in the expression of CD11b, CD14, C3aR, C5aR1, TLR2, and TLR4 markers in leukocytes. Inhibition of component C3 by compstatin significantly reduced the production of anaphylatoxins and the Terminal Complement Complex (TCC) in blood plasma treated with the toxin, as well as the expression of CD11b, C3aR, and C5aR on leukocytes. C-SVMP was able to induce increased production of the cytokines IL-1β and IL-6 and the chemokines CXCL8/IL-8, CCL2/MCP-1, and CXCL9/MIG in the human whole blood model. The addition of compstatin to the reactions caused a significant reduction in the production of IL-1β, CXCL8/IL-8, and CCL2/MCP-1 in cells treated with C-SVMP. We therefore conclude that C-SVMP is able to activate the complement system, which leads to an increase in the inflammatory process. The data obtained with the use of compstatin indicate that complement inhibition may significantly control the inflammatory process initiated by Bothrops snake venom toxins.

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Section: Introductionmentioning

confidence: 99%

Complement System Inhibition Modulates the Pro-Inflammatory Effects of a Snake Venom Metalloproteinase

et al. 2019

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“…The so-called cobra venom factor (CVF), isolated from N. naja [ 167 ], as well as L-AAO and serine protease from snakes of the genus Bothrops [ 168 ], have a complement-activating effect and have been used in the study of the complement cascade. CVF acts as a C3 analog able to deplete complement and is used in animal experiments to determine the role of the complement cascade in diverse pathological conditions, such as reperfusion injury [ 169 ], age-related macular degeneration [ 170 ], paroxysmal nocturnal hemoglobinuria [ 171 ] or myasthenia gravis [ 172 ].…”

Section: Myotoxinsmentioning

confidence: 99%

Biomedical applications of snake venom: from basic science to autoimmunity and rheumatology

Cañas

Castaño-Valencia

Castro-Herrera

et al. 2021

Journal of Translational Autoimmunity

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Snake venoms have components with diverse biological actions that are extensively studied to identify elements that may be useful in biomedical sciences. In the field of autoimmunity and rheumatology, various findings useful for the study of diseases and potential drug development have been reported. The study of disintegrins, proteins that block the action of integrins, has been useful for the development of antiplatelet agents and principles for the development of immunosuppressants and antineoplastics. Several proteins in snake venoms act on the coagulation cascade, activating factors that have allowed the development of tests for the study of coagulation, including Russell’s viper venom time, which is useful in the diagnosis of antiphospholipid syndrome. Neurotoxins with either pre- or postsynaptic effects have been used to study neurogenic synapses and neuromuscular plaques and the development of analgesics, muscle relaxants and drugs for neurodegenerative diseases. Various components act by inhibiting cells and proteins of the immune system, which will allow the development of anti-inflammatory and immunosuppressive drugs. This review summarizes the usefulness of the components of snake venoms in the fields of autoimmunity and rheumatology, which can serve as a basis for diverse translational research.

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“…103 Snake venom-derived serine proteases include flavoxobin. 104 Komodo dragon (Varanus komodoensis) venom capable of shock induction is a kallikrein-type serine protease as well. 105 Fish viscera contain this enzyme, in its variations such as trypsin, chymotrypsin and elastase.…”

Section: Snakes and Other Vertebratesmentioning

confidence: 99%

A critical review on serine protease: Key immune manipulator and pathology mediator

Patel

2017

Allergologia et Immunopathologia

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Proteolytic activity is fundamental to survival, so it is not surprising that all living organisms have proteases, especially seine protease. This enzyme in its numerous isoforms and homologues, constitutes the quintessential offence and defence factors, in the form of surface proteins, secreted molecules, gut digestive enzymes, venom in specialised glands or plant latex, among other manifestations. Occurring as trypsin, chymotrypsin, elastase, collagenase, thrombin, subtilisin etc., it mediates a diverse array of functions, including pathological roles as inflammatory, coagulatory to haemorrhagic. This review emphasizes that despite the superficial differences in mechanisms, most health issues, be they infectious, allergic, metabolic, or neural have a common conduit. This enzyme, in its various glycosylated forms leads to signal misinterpretations, wreaking havoc. However, organisms are endowed with serine protease inhibitors which might restrain this ubiquitous yet deleterious enzyme. Hence, serine proteases-driven pathogenesis and antagonising role of inhibitors is the focal point of this critical review.

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Bothrops snake venoms and their isolated toxins, an L-amino acid oxidase and a serine protease, modulate human complement system pathways

Cited by 22 publications

References 37 publications

Complement System Inhibition Modulates the Pro-Inflammatory Effects of a Snake Venom Metalloproteinase

Complement System Inhibition Modulates the Pro-Inflammatory Effects of a Snake Venom Metalloproteinase

Biomedical applications of snake venom: from basic science to autoimmunity and rheumatology

A critical review on serine protease: Key immune manipulator and pathology mediator

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