C-Reactive Protein Promotes Inflammation through FcγR-Induced Glycolytic Reprogramming of Human Macrophages.

Autor:	Newling M; Department of Rheumatology and Clinical Immunology, Academic Medical Center, Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands., Sritharan L; Department of Rheumatology and Clinical Immunology, Academic Medical Center, Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands., van der Ham AJ; Department of Parasitology, Leiden University Medical Center, University of Leiden, 2333 ZA Leiden, the Netherlands., Hoepel W; Department of Rheumatology and Clinical Immunology, Academic Medical Center, Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands., Fiechter RH; Department of Rheumatology and Clinical Immunology, Academic Medical Center, Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands.; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands., de Boer L; Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; and., Zaat SAJ; Department of Medical Microbiology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; and., Bisoendial RJ; Division of Rheumatology, Maasstad Hospital, 3079 DZ Rotterdam, the Netherlands., Baeten DLP; Department of Rheumatology and Clinical Immunology, Academic Medical Center, Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands., Everts B; Department of Parasitology, Leiden University Medical Center, University of Leiden, 2333 ZA Leiden, the Netherlands., den Dunnen J; Department of Rheumatology and Clinical Immunology, Academic Medical Center, Amsterdam Rheumatology and Immunology Center, Amsterdam, the Netherlands; j.dendunnen@amsterdamumc.nl.; Department of Experimental Immunology, Amsterdam Infection and Immunity Institute, Amsterdam University Medical Centers, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Jul 01; Vol. 203 (1), pp. 225-235. Date of Electronic Publication: 2019 May 22.
DOI:	10.4049/jimmunol.1900172
Abstrakt:	C-reactive protein (CRP) is an acute-phase protein produced in high quantities by the liver in response to infection and during chronic inflammatory disorders. Although CRP is known to facilitate the clearance of cell debris and bacteria by phagocytic cells, the role of CRP in additional immunological functions is less clear. This study shows that complexed CRP (phosphocholine [PC]:CRP) (formed by binding of CRP to PC moieties), but not soluble CRP, synergized with specific TLRs to posttranscriptionally amplify TNF, IL-1β, and IL-23 production by human inflammatory macrophages. We identified FcγRI and IIa as the main receptors responsible for initiating PC:CRP-induced inflammation. In addition, we identified the underlying mechanism, which depended on signaling through kinases Syk, PI3K, and AKT2, as well as glycolytic reprogramming. These data indicate that in humans, CRP is not only a marker but also a driver of inflammation by human macrophages. Therefore, although providing host defense against bacteria, PC:CRP-induced inflammation may also exacerbate pathology in the context of disorders such as atherosclerosis. (Copyright © 2019 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu