C-reactive protein-mediated phagocytosis and phospholipase D signalling through the high-affinity receptor for immunoglobulin G (FcgammaRI).
C-reactive protein (CRP) is the prototypic acute-phase protein in man which performs innate immune functions. CRP-mediated phagocytosis may be indirect, through activation of complement and complement receptors, or direct, through receptors for the Fc portion of immunoglobulin G (IgG; FcgammaRs) or even a putative CRP-specific receptor. No strong evidence has been shown to indicate which receptors may be responsible for phagocytosis or signalling responses. Using BIAcore technology, we confirm that CRP binds directly to the extracellular portion of FcgammaRI with a threefold higher affinity than IgG (KD = 0.81 x 10-9 m). Binding is Ca2+ dependent and is inhibited by IgG1 but not by phosphorylcholine (PC). CRP opsonization (using CRP concentrations within the normal human serum range) of PC-conjugated sheep erythrocytes increased phagocytosis of these particles by COS-7 cells transfected with FcgammaRI-II chimaera or FcgammaRI/gamma-chain. Interferon-gamma-treated U937 cells, which signal through FcgammaRI to activate phospholipase D (PLD) in response to cross-linked IgG, were also activated by CRP without any requirement for further cross-linking. These studies indicate that CRP is capable of binding to and cross-linking FcgammaRI thereby resulting in PLD activation and increased phagocytosis. Uptake by FcgammaRI has been reported to promote various acquired immune responses suggesting that CRP could act in a similar way.
Bodman-Smith
Katherine B
KB
Immunology Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK. kikki.bodman-smith@lshtm.ac.uk
Melendez
Alirio J
AJ
Campbell
Ian
I
Harrison
Patrick T
PT
Allen
Janet M
JM
Raynes
John G
JG
D000818:Animals; D001667:Binding, Competitive; D002097:C-Reactive Protein / Q000276:immunology* / Q000378:metabolism; D019556:COS Cells; D002118:Calcium / Q000502:physiology; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D010739:Phospholipase D / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D012397:Rosette Formation; D012756:Sheep; D015398:Signal Transduction / Q000276:immunology; D020298:U937 Cells
D007074:Immunoglobulin G; D017452:Receptors, IgG; D002097:C-Reactive Protein; D010739:Phospholipase D; D002118:Calcium