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The role of complement inhibitors beyond controlling inflammation
Author(s) -
Blom A. M.
Publication year - 2017
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12606
Subject(s) - complement system , complement membrane attack complex , complement control protein , endoplasmic reticulum , microbiology and biotechnology , intracellular , extracellular , complement (music) , inflammation , biology , classical complement pathway , immunology , immune system , biochemistry , phenotype , gene , complementation
The complement system is an arm of innate immunity that aids in the removal of pathogens and dying cells. Due to its harmful, pro‐inflammatory potential, complement is controlled by several soluble and membrane‐bound inhibitors. This family of complement regulators has been recently extended by the discovery of several new members, and it is becoming apparent that these proteins harbour additional functions. In this review, the current state of knowledge of the physiological functions of four complement regulators will be described: cartilage oligomeric matrix protein ( COMP ), CUB and sushi multiple domains 1 ( CSMD 1), sushi domain‐containing protein 4 ( SUSD 4) and CD 59. Complement activation is involved in both the development of and defence against cancer. COMP expression is pro‐oncogenic, whereas CSMD 1 and SUSD 4 act as tumour suppressors. These effects may be related in part to the complex influence of complement on cancer but also depend on unrelated functions such as the protection of cells from endoplasmic reticulum stress conveyed by intracellular COMP . CD 59 is the main inhibitor of the membrane attack complex, and its deficiency leads to complement attack on erythrocytes and severe haemolytic anaemia, which is now amenable to treatment with an inhibitor of C5 cleavage. Unexpectedly, the intracellular pool of CD 59 is crucial for insulin secretion from pancreatic β‐cells. This finding is one of several relating to the intracellular functions of complement proteins, which until recently were only considered to be present in the extracellular space. Understanding the alternative functions of complement inhibitors may unravel unexpected links between complement and other physiological systems, but is also important for better design of therapeutic complement inhibition.