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Merle NS, Church SE, Fremeaux-Bacchi V, et al. Complement System Part I - Molecular Mechanisms of Activation and Regulation. Front Immunol. 2015;6:262doi: 10.3389/fimmu.2015.00262.
Merle, N. S., Church, S. E., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015). Complement System Part I - Molecular Mechanisms of Activation and Regulation. Frontiers in immunology, 6262. https://doi.org/10.3389/fimmu.2015.00262
Merle, Nicolas S, et al. "Complement System Part I - Molecular Mechanisms of Activation and Regulation." Frontiers in immunology vol. 6 (2015): 262. doi: https://doi.org/10.3389/fimmu.2015.00262
Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement System Part I - Molecular Mechanisms of Activation and Regulation. Front Immunol. 2015 Jun 02;6:262. doi: 10.3389/fimmu.2015.00262. eCollection 2015. PMID: 26082779; PMCID: PMC4451739.
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Front Immunol. 2015 Jun 02;6:262. doi: 10.3389/fimmu.2015.00262. eCollection 2015.

Complement System Part I - Molecular Mechanisms of Activation and Regulation.

Frontiers in immunology

Nicolas S Merle, Sarah Elizabeth Church, Veronique Fremeaux-Bacchi, Lubka T Roumenina

Affiliations

  1. UMR_S 1138, Cordeliers Research Center, Complement and Diseases Team, INSERM , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Paris Cité, Université Paris Descartes , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université Pierre et Marie Curie-Paris , Paris , France.
  2. UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Paris Cité, Université Paris Descartes , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université Pierre et Marie Curie-Paris , Paris , France ; UMR_S 1138, Cordeliers Research Center, Integrative Cancer Immunology Team, INSERM , Paris , France.
  3. UMR_S 1138, Cordeliers Research Center, Complement and Diseases Team, INSERM , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Paris Cité, Université Paris Descartes , Paris , France ; UMR_S 1138, Centre de Recherche des Cordeliers, Sorbonne Universités, Université Pierre et Marie Curie-Paris , Paris , France ; Service d'Immunologie Biologique, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges-Pompidou , Paris , France.

PMID: 26082779 PMCID: PMC4451739 DOI: 10.3389/fimmu.2015.00262

Abstract

Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here, we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical, and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins, and the membrane-attack-complex. We will also discuss the importance of structure-function relationships using the example of atypical hemolytic uremic syndrome. Lastly, we will discuss the development and benefits of therapies using complement inhibitors.

Keywords: alternative complement pathway; anaphylatoxins; classical complement pathway; complement regulatory proteins; complement system proteins; endothelial cells; membrane-attack-complex; structure–function relationships

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