Journal
BIOLOGICAL CHEMISTRY
Volume 402, Issue 9, Pages 1129-1145Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2021-0209
Keywords
acute-phase response; alpha-1-acid-glycoprotein; alpha-2-macroglobulin; hepatocyte; inflammation; serum amyloid A
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Funding
- Deutsche Forschungsgemeinschaft [SFB 974, 190586431]
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The expression of acute-phase proteins plays a crucial role in maintaining homeostasis, tissue repair, and the organism's defense strategy, particularly in the context of innate immunity. Inflammatory responses lead to significant changes in serum protein composition, which can be used diagnostically. The liver, as the main site of APP synthesis, is constantly exposed to antigens or pathogens through blood flow, as well as systemic inflammatory signals.
The expression of acute-phase proteins (APP's) maintains homeostasis and tissue repair, but also represents a central component of the organism's defense strategy, especially in the context of innate immunity. Accordingly, an inflammatory response is accompanied by significant changes in the serum protein composition, an aspect that is also used diagnostically. As the main site of APP synthesis the liver is constantly exposed to antigens or pathogens via blood flow, but also to systemic inflammatory signals originating either from the splanchnic area or from the circulation. Under both homeostatic and acutephase response (APR) conditions the composition of APP's is determined by the pattern of regulatory mediators derived from the systemic circulation or from local cell populations, especially liver macrophages. The key regulators mentioned here most frequently are IL-1 beta, IL-6 and TNF-alpha. In addition to a variety of molecular mediators described mainly on the basis of in vitro studies, recent data emphasize the in vivo relevance of cellular key effectors as well as molecular key mediators and protein modifications for the regulation and function of APP's. These are aspects, on which the present review is primarily focused.
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