FcgammaRIIa is a target for modulation by TNFalpha in human neutrophils.
Activation of neutrophils by the interaction of immune complexes with Fc gamma receptors (FcgammaR) is amplified in tumor necrosis factor-alpha (TNFalpha)-primed cells, whereas interleukin-10 (IL-10) has been reported to suppress cytokine-mediated neutrophil activation. We examined whether the expression and function of FcgammaR in human neutrophils is modulated by TNFalpha and IL-10 in vitro, and whether FcgammaRIIa expression is altered following treatment with the TNFalpha inhibitor infliximab in rheumatoid arthritis (RA) patients in vivo. TNFalpha treatment induced upregulation of expression and function of the major activating Fc receptor, FcgammaRIIa, in neutrophils from healthy donors. Unexpectedly, treatment with IL-10 led to gain of FcgammaRIIa function in TNFalpha-primed neutrophils. In neutrophils from RA patients initiating infliximab therapy and followed longitudinally through consecutive treatments, FcgammaRIIa protein decreased during the course of TNFalpha blockade, indicating that FcgammaRIIa is a target of TNFalpha modulation in human neutrophils in vivo.
Belostocki
Kristina
K
Hospital for Special Surgery, Weill Medical College of Cornell University, Department of Medicine and Research Division, New York, NY 10021, USA.
Park
Mee-Soon
MS
Redecha
Patricia B
PB
Masuda
Emi
E
Salmon
Jane E
JE
Pricop
Luminita
L
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD / Q000187:drug effects* / Q000276:immunology*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D015153:Blotting, Western; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D000069285:Infliximab; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D017452:Receptors, IgG / Q000187:drug effects* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018501:Antirheumatic Agents; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000069285:Infliximab