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C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera
Systemic complement activation drives a plethora of pathological conditions, but its role in snake envenoming remains obscure. Here, we explored complement’s contribution to the physiopathogenesis of Naja annulifera envenomation. We found that N. annulifera venom promoted the generation of C3a, C4a,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082402/ https://www.ncbi.nlm.nih.gov/pubmed/33936074 http://dx.doi.org/10.3389/fimmu.2021.652242 |
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author | Silva de França, Felipe Villas-Boas, Isadora Maria Cogliati, Bruno Woodruff, Trent M. Reis, Edimara da Silva Lambris, John D. Tambourgi, Denise V. |
author_facet | Silva de França, Felipe Villas-Boas, Isadora Maria Cogliati, Bruno Woodruff, Trent M. Reis, Edimara da Silva Lambris, John D. Tambourgi, Denise V. |
author_sort | Silva de França, Felipe |
collection | PubMed |
description | Systemic complement activation drives a plethora of pathological conditions, but its role in snake envenoming remains obscure. Here, we explored complement’s contribution to the physiopathogenesis of Naja annulifera envenomation. We found that N. annulifera venom promoted the generation of C3a, C4a, C5a, and the soluble Terminal Complement Complex (sTCC) mediated by the action of snake venom metalloproteinases. N. annulifera venom also induced the release of lipid mediators and chemokines in a human whole-blood model. This release was complement-mediated, since C3/C3b and C5a Receptor 1 (C5aR1) inhibition mitigated the effects. In an experimental BALB/c mouse model of envenomation, N. annulifera venom promoted lipid mediator and chemokine production, neutrophil influx, and swelling at the injection site in a C5a-C5aR1 axis-dependent manner. N. annulifera venom induced systemic complementopathy and increased interleukin and chemokine production, leukocytosis, and acute lung injury (ALI). Inhibition of C5aR1 with the cyclic peptide antagonist PMX205 rescued mice from these systemic reactions and abrogated ALI development. These data reveal hitherto unrecognized roles for complement in envenomation physiopathogenesis, making complement an interesting therapeutic target in envenomation by N. annulifera and possibly by other snake venoms. |
format | Online Article Text |
id | pubmed-8082402 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80824022021-04-30 C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera Silva de França, Felipe Villas-Boas, Isadora Maria Cogliati, Bruno Woodruff, Trent M. Reis, Edimara da Silva Lambris, John D. Tambourgi, Denise V. Front Immunol Immunology Systemic complement activation drives a plethora of pathological conditions, but its role in snake envenoming remains obscure. Here, we explored complement’s contribution to the physiopathogenesis of Naja annulifera envenomation. We found that N. annulifera venom promoted the generation of C3a, C4a, C5a, and the soluble Terminal Complement Complex (sTCC) mediated by the action of snake venom metalloproteinases. N. annulifera venom also induced the release of lipid mediators and chemokines in a human whole-blood model. This release was complement-mediated, since C3/C3b and C5a Receptor 1 (C5aR1) inhibition mitigated the effects. In an experimental BALB/c mouse model of envenomation, N. annulifera venom promoted lipid mediator and chemokine production, neutrophil influx, and swelling at the injection site in a C5a-C5aR1 axis-dependent manner. N. annulifera venom induced systemic complementopathy and increased interleukin and chemokine production, leukocytosis, and acute lung injury (ALI). Inhibition of C5aR1 with the cyclic peptide antagonist PMX205 rescued mice from these systemic reactions and abrogated ALI development. These data reveal hitherto unrecognized roles for complement in envenomation physiopathogenesis, making complement an interesting therapeutic target in envenomation by N. annulifera and possibly by other snake venoms. Frontiers Media S.A. 2021-04-15 /pmc/articles/PMC8082402/ /pubmed/33936074 http://dx.doi.org/10.3389/fimmu.2021.652242 Text en Copyright © 2021 Silva de França, Villas-Boas, Cogliati, Woodruff, Reis, Lambris and Tambourgi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Silva de França, Felipe Villas-Boas, Isadora Maria Cogliati, Bruno Woodruff, Trent M. Reis, Edimara da Silva Lambris, John D. Tambourgi, Denise V. C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera |
title | C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera
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title_full | C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera
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title_fullStr | C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera
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title_full_unstemmed | C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera
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title_short | C5a-C5aR1 Axis Activation Drives Envenomation Immunopathology by the Snake Naja annulifera
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title_sort | c5a-c5ar1 axis activation drives envenomation immunopathology by the snake naja annulifera |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082402/ https://www.ncbi.nlm.nih.gov/pubmed/33936074 http://dx.doi.org/10.3389/fimmu.2021.652242 |
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