4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Complement activation, regulation, and molecular basis for complement‐related diseases

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The complement system is an essential element of the innate immune response that becomes activated upon recognition of molecular patterns associated with microorganisms, abnormal host cells, and modified molecules in the extracellular environment. The resulting proteolytic cascade tags the complement activator for elimination and elicits a pro‐inflammatory response leading to recruitment and activation of immune cells from both the innate and adaptive branches of the immune system. Through these activities, complement functions in the first line of defense against pathogens but also contributes significantly to the maintenance of homeostasis and prevention of autoimmunity. Activation of complement and the subsequent biological responses occur primarily in the extracellular environment. However, recent studies have demonstrated autocrine signaling by complement activation in intracellular vesicles, while the presence of a cytoplasmic receptor serves to detect complement‐opsonized intracellular pathogens. Furthermore, breakthroughs in both functional and structural studies now make it possible to describe many of the intricate molecular mechanisms underlying complement activation and the subsequent downstream events, as well as its cross talk with, for example, signaling pathways, the coagulation system, and adaptive immunity. We present an integrated and updated view of complement based on structural and functional data and describe the new roles attributed to complement. Finally, we discuss how the structural and mechanistic understanding of the complement system rationalizes the genetic defects conferring uncontrolled activation or other undesirable effects of complement.

          Related collections

          Author and article information

          Journal
          EMBO J
          EMBO J
          10.1002/(ISSN)1460-2075
          EMBJ
          embojnl
          The EMBO Journal
          John Wiley and Sons Inc. (Hoboken )
          0261-4189
          1460-2075
          21 October 2015
          12 November 2015
          : 34
          : 22 ( doiID: 10.1002/embj.v34.22 )
          : 2735-2757
          Affiliations
          [ 1 ] Department of Molecular Biology and Genetics Aarhus University Aarhus Denmark
          [ 2 ] Department of Biomedicine Aarhus University Aarhus Denmark
          [ 3 ] Program in Cellular and Molecular Medicine Children's Hospital Boston MA USA
          Author notes
          [* ] Corresponding author. Tel: +45 87167851; E‐mail: st@ 123456biomed.au.dk

          Corresponding author. Tel: +45 51446530; E‐mail: gra@ 123456mbg.au.dk

          Article
          PMC4682646 PMC4682646 4682646 EMBJ201591881
          10.15252/embj.201591881
          4682646
          26489954
          © 2015 The Authors
          Page count
          Pages: 23
          Funding
          Funded by: LUNA Nanomedicine Center
          Funded by: The Lundbeck Foundation
          Funded by: Danish Science Research Council
          Funded by: Danish Council for Independent Research, Medical Sciences
          Funded by: Novo‐Nordisk Foundation
          Funded by: Marie Curie International Outgoing Fellowship
          Funded by: 7th European Community Framework Programme
          Categories
          Review
          Review
          Custom metadata
          2.0
          embj201591881
          12 November 2015
          Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.2 mode:remove_FC converted:09.12.2015

          Comments

          Comment on this article