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Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity

In the complement system, C3 is a central component in complement activation, immune defense and immune regulation. In all pathways of complement activation, the pivotal step is conversion of the component C3 to C3b and C3a, which is responsible to eliminate the pathogen and opsonization. In this st...

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Autores principales: Wu, Meng, Jia, Bei-bei, Li, Mo-fei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913944/
https://www.ncbi.nlm.nih.gov/pubmed/35281048
http://dx.doi.org/10.3389/fimmu.2022.813173
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author Wu, Meng
Jia, Bei-bei
Li, Mo-fei
author_facet Wu, Meng
Jia, Bei-bei
Li, Mo-fei
author_sort Wu, Meng
collection PubMed
description In the complement system, C3 is a central component in complement activation, immune defense and immune regulation. In all pathways of complement activation, the pivotal step is conversion of the component C3 to C3b and C3a, which is responsible to eliminate the pathogen and opsonization. In this study, we examined the immunological properties of C3 and its activated fragment C3a from Japanese flounder (Paralichthys olivaceus) (PoC3 and PoC3a), a teleost species with important economic value. PoC3 is composed of 1655 amino acid residues, contains the six domains and highly conserved GCGEQ sequence of the C3 family. We found that PoC3 expression occurred in nine different tissues and was upregulated by bacterial challenge. In serum, PoC3 was able to bind to a broad-spectrum of bacteria, and purified native PoC3 could directly kill specific pathogen. When PoC3 expression in Japanese flounder was knocked down by siRNA, serum complement activity was significantly decreased, and bacterial replication in fish tissues was significantly increased. Recombinant PoC3a (rPoC3a) exhibited apparent binding capacities to bacteria and Japanese flounder peripheral blood leukocytes (PBL) and induce chemotaxis of PBL. Japanese flounder administered rPoC3a exhibited enhanced resistance against bacterial infection. Taken together, these results indicate that PoC3 is likely a key factor of complement activation, and PoC3 and PoC3a are required for optimal defense against bacterial infection in teleost.
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spelling pubmed-89139442022-03-12 Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity Wu, Meng Jia, Bei-bei Li, Mo-fei Front Immunol Immunology In the complement system, C3 is a central component in complement activation, immune defense and immune regulation. In all pathways of complement activation, the pivotal step is conversion of the component C3 to C3b and C3a, which is responsible to eliminate the pathogen and opsonization. In this study, we examined the immunological properties of C3 and its activated fragment C3a from Japanese flounder (Paralichthys olivaceus) (PoC3 and PoC3a), a teleost species with important economic value. PoC3 is composed of 1655 amino acid residues, contains the six domains and highly conserved GCGEQ sequence of the C3 family. We found that PoC3 expression occurred in nine different tissues and was upregulated by bacterial challenge. In serum, PoC3 was able to bind to a broad-spectrum of bacteria, and purified native PoC3 could directly kill specific pathogen. When PoC3 expression in Japanese flounder was knocked down by siRNA, serum complement activity was significantly decreased, and bacterial replication in fish tissues was significantly increased. Recombinant PoC3a (rPoC3a) exhibited apparent binding capacities to bacteria and Japanese flounder peripheral blood leukocytes (PBL) and induce chemotaxis of PBL. Japanese flounder administered rPoC3a exhibited enhanced resistance against bacterial infection. Taken together, these results indicate that PoC3 is likely a key factor of complement activation, and PoC3 and PoC3a are required for optimal defense against bacterial infection in teleost. Frontiers Media S.A. 2022-02-25 /pmc/articles/PMC8913944/ /pubmed/35281048 http://dx.doi.org/10.3389/fimmu.2022.813173 Text en Copyright © 2022 Wu, Jia and Li 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
Wu, Meng
Jia, Bei-bei
Li, Mo-fei
Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity
title Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity
title_full Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity
title_fullStr Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity
title_full_unstemmed Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity
title_short Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity
title_sort complement c3 and activated fragment c3a are involved in complement activation and anti-bacterial immunity
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8913944/
https://www.ncbi.nlm.nih.gov/pubmed/35281048
http://dx.doi.org/10.3389/fimmu.2022.813173
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