Intracellular complement activation—An alarm raising mechanism?

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http://hdl.handle.net/10138/292426

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Reichhardt , M P & Meri , S 2018 , ' Intracellular complement activation—An alarm raising mechanism? ' , Seminars in immunology , vol. 38 , pp. 54-62 . https://doi.org/10.1016/j.smim.2018.03.003

Title: Intracellular complement activation—An alarm raising mechanism?
Author: Reichhardt, M.P.; Meri, S.
Contributor: University of Helsinki, HUSLAB
Date: 2018-08
Language: eng
Number of pages: 9
Belongs to series: Seminars in immunology
ISSN: 1044-5323
URI: http://hdl.handle.net/10138/292426
Abstract: Abstract It has become increasingly apparent that the complement system, being an ancient defense mechanism, is not operative only in the extracellular milieu but also intracellularly. In addition to the known synthetic machinery in the liver and by macrophages, many other cell types, including lymphocytes, adipocytes and epithelial cells produce selected complement components. Activation of e.g. C3 and C5 inside cells may have multiple effects ranging from direct antimicrobial defense to cell differentiation and possible influence on metabolism. Intracellular activation of C3 and C5 in T cells is involved in the maintenance of immunological tolerance and promotes differentiation of T helper cells into Th1-type cells that activate cell-mediated immune responses. Adipocytes are unique in producing many complement sensor proteins (like C1q) and Factor D (adipsin), the key enzyme in promoting alternative pathway amplification. The effects of complement activation products are mediated by intracellular and cell membrane receptors, like C3aR, C5aR1, C5aR2 and the complement regulator MCP/CD46, often jointly with other receptors like the T cell receptor, Toll-like receptors and those of the inflammasomes. These recent observations link complement activation to cellular metabolic processes, intracellular defense reactions and to diverse adaptive immune responses. The complement components may thus be viewed as intracellular alarm molecules involved in the cellular danger response.
Subject: Intracellular complement
C3
C5
C3a
C5a
Inflammasome
Complement
C5aR1
C5aR2
Metabolism
Cellular homeostasis
Complement signaling
Intracellular defense
Adaptive immunology
3111 Biomedicine
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