| 1. |
- Okrój, Marcin, et al.
(author)
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C4b-Binding Protein
- 2017
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In: The Complement FactsBook : Second Edition - Second Edition. - 9780128104200 ; , s. 251-259
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Book chapter (peer-reviewed)abstract
- C4b-binding protein (C4BP) is the main fluid-phase inhibitor of the classical complement pathway. It serves as cofactor in factor I-mediated cleavage of C4b and C3b and it accelerates the decay of complement convertases. The main role of C4BP is to prevent overt complement-mediated inflammation both in solution and on self-molecules recognised by C1q, such as amyloid. Furthermore, C4BP is frequently recruited onto the surface of various pathogens, which allows these to evade immune response. The main isoform of C4BP has a oligomeric structure and consists of seven chains, which confer complement inhibitory activity, and a single chain, which binds anticoagulant protein S and docks the molecule to negatively charged phospholipids exposed, e.g., on the surface of dying cells. Both α- and β- chains are built from complement control protein (CCP) domains typical of complement inhibitors. C4BP is one of the acute-phase proteins and its expression is upregulated by proinflammatory cytokines.
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| 2. |
- Okrój, Marcin, et al.
(author)
-
Factor I
- 2017
-
In: The Complement FactsBook : Second Edition - Second Edition. - 9780128104200 ; , s. 147-154
-
Book chapter (peer-reviewed)abstract
- Factor I (FI) is a serine protease with narrow specificity restricted to activated complement components C3b and C4b. Supported by appropriate cofactors such as factor H or C4b-binding protein, FI cleaves peptide bonds in C3b/C4b after arginyl residues. By doing so it inhibits further propagation of the complement cascade thus contributing to protection from misguided or excessive complement attack on own cells and tissues. Furthermore, inactivated fragments of C3b bind to specific receptors on immune cells and influence their function such as phagocytosis. Production and secretion of FI into bloodstream is mainly supported by liver but extrahepatic sources were also identified, such as keratinocytes, fibroblasts, monocytes and endothelial cells. Mutations/polymorphism in FI may diminish its secretion or cause loss of function. When leading to complete deficiency, alterations in FI markedly distort the balance between complement activation and inhibition. The outcome is increased rate of bacterial infections and glomerulonephritis. Partial deficiency of FI predisposes to atypical haemolytic uraemic syndrome or age-related macular degeneration.
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| 3. |
- Su, Shanice Yc, et al.
(author)
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Chapter 33 - Vitronectin
- 2017. - 2
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In: The Complement Factsbook, Second Edition. - 9780128104200 - 9780128104217 ; 1, s. 351-360
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Book chapter (pop. science, debate, etc.)
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| 4. |
- Su, Yu Ching, et al.
(author)
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Vitronectin
- 2017
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In: The Complement FactsBook : Second Edition - Second Edition. - 9780128104200 ; , s. 351-360
-
Book chapter (peer-reviewed)abstract
- The multifaceted complement regulator vitronectin (Vn) can be found in almost all tissues of the human body. It is primarily produced by the liver and is thus detected at high concentrations in plasma. Upon inflammation, Vn is upregulated revealing its importance for the innate immune defence against danger signals. It consists of 459 amino acids and has several key sequences linked to its functions. Vn interacts at its N-terminal with plasminogen activator inhibitor-1 and urokinase-type plasminogen activator receptor (uPAR). Downstream of these binding sites are sequences that attract integrins and collagen in addition to the thrombin-antithrombin III complex. Heme-binding plasma proteins, as well as plasminogen, can also interact with Vn through heparin-binding domains. One of the main functions of Vn is to inhibit the terminal pathway of the complement system by preventing formation of the lethal pore-forming complex. This chapter will in detail discuss the knowledge on this important molecule.
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