Recognition and functional activation of the human IgA receptor (FcalphaRI) by C-reactive protein.

Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 03/2011; 108(12):4974-9. DOI: 10.1073/pnas.1018369108
Source: PubMed

ABSTRACT C-reactive protein (CRP) is an important biomarker for inflammatory diseases. However, its role in inflammation beyond complement-mediated pathogen clearance remains poorly defined. We identified the major IgA receptor, FcαRI, as a ligand for pentraxins. CRP recognized FcαRI both in solution and on cells, and the pentraxin binding site on the receptor appears distinct from that recognized by IgA. Further competitive binding and mutational analysis showed that FcαRI bound to the effector face of CRP in a region overlapping with complement C1q and Fcγ receptor (FcγR) binding sites. CRP cross-linking of FcαRI resulted in extracellular signal-regulated kinase (ERK) phosphorylation, cytokine production, and degranulation in FcαRI-transfected RBL cells. In neutrophils, CRP induced FcαRI surface expression, phagocytosis, and TNF-α secretion. The ability of CRP to activate FcαRI defines a function for pentraxins in inflammatory responses involving neutrophils and macrophages. It also highlights the innate aspect of otherwise humoral immunity-associated antibody receptors.

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Available from: Terry Du Clos, Jul 01, 2015
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