Recognition and functional activation of the human IgA receptor (FcαRI) by C-reactive protein
| Autor: | Peter D. Sun, Ruipeng Wang, Lorraine L. Marnell, Jinghua Lu, Terry W. Du Clos, Kristopher D. Marjon, Carolyn Mold |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Pentraxin binding
Neutrophils medicine.medical_treatment Inflammation Receptors Fc Phagocytosis Antigens CD medicine Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases Receptor Binding Sites Multidisciplinary Pentraxins biology Tumor Necrosis Factor-alpha Complement C1q Macrophages Receptors IgG Degranulation Biological Sciences Immunity Innate C-Reactive Protein Cytokine Mutation Immunology biology.protein Tumor necrosis factor alpha medicine.symptom Antibody Biomarkers Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:4974-4979 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1018369108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|