Differentiation of the human monocyte cell line, U937, with dibutyryl cyclicAMP induces the expression of the inhibitory Fc receptor, FcgammaRIIb.
FC receptor for IgG receptor (Fcgamma) mediated activation of macrophages is essential for the clearance of immune complexes and control of inflammation. However, activated macrophages play an integral role in tissue destruction associated with autoimmune and inflammatory disease processes. Understanding the mechanisms which balance activating and inhibitory signals generated by immune complexes are therefore of critical importance to human disease. Here, we demonstrate that differentiation of the human monocytic U937 cell line to a macrophage phenotype with dibutyryl cyclicAMP induces both mRNA and protein expression of the inhibitory IgG receptor, FcgammaRIIb1. We further demonstrate that, following receptor aggregation, FcgammaRII transiently recruits the 5'-inositol phosphatase, SHIP. These data define a role for FcgammaRIIb in the modulation of immune complex mediated macrophage activation in a human model system.
Cameron
Angus J M
AJ
Department of Medicine & Therapeutics, Division of Biochemistry & Molecular Biology, University of Glasgow, Glasgow G12 8QQ, Scotland, UK. a.cameron@bio.gla.ac.uk
McDonald
Kenneth J
KJ
Harnett
Margaret M
MM
Allen
Janet M
JM
D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D008262:Macrophage Activation / Q000276:immunology / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011961:Receptors, Fc / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; C499173:FCGR2B protein, human; C080571:Fc gamma receptor IIB; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D003994:Bucladesine; D010744:Phosphoric Monoester Hydrolases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases