TY - JOUR
T1 - Human Neutrophil Fcγ Receptors Initiate and Play Specialized Nonredundant Roles in Antibody-Mediated Inflammatory Diseases
AU - Tsuboi, Naotake
AU - Asano, Kenichi
AU - Lauterbach, Michael
AU - Mayadas, Tanya N.
N1 - Funding Information:
The human MRP8 promoter construct was kindly provided by E. Lagasse (University of Pittsburgh, PA), and I.L. Weissman (Stanford University, CA). We are grateful to M. Minami (Brigham and Women's Hospital) for assistance with quantitative PCR analysis. We thank L. Xiao and G. Stavrakis for excellent technical assistance. This work was supported by an Arthritis Foundation postdoctoral fellowship (N.T.), a travel grant from Mitsukoshi Health and Welfare Foundation (K.A.), and NIH RO1 HL065095 and AR050800 (T.N.M). Author contributions: N.T. and K.A. designed and performed the research, analyzed the data and wrote the paper, ML performed the research and analyzed the data, and T.N.M. designed the research and wrote the paper.
PY - 2008/6/13
Y1 - 2008/6/13
N2 - Inflammation mediated by antibody-antigen complexes contributes to autoimmune diseases. Mice deficient in the common Fcγ-chain are protected from IgG-mediated glomerulonephritis and the reverse passive Arthus (RPA) reaction and FcR-bearing macrophages, and mast cells have been assigned primary roles in these processes. Here we demonstrate that neutrophil-selective transgenic expression of the two uniquely human neutrophil Fc gamma receptors (FcγRs), FcγRIIA and FcγRIIIB, in Fcγ-chain-deficient mice restored susceptibility to progressive glomerulonephritis and the cutaneous RPA reaction. FcγRIIIB and FcγRIIA mediated neutrophil accumulation, whereas FcγRIIA alone promoted organ injury. In a model of soluble immune complexes deposited within the vasculature, FcγRIIIB was responsible for neutrophil slow rolling and adhesion whereas in the cremaster RPA, induced by both vascular and tissue soluble immune complexes, FcγRIIA predominated. Thus, human FcγRs on neutrophils serve as molecular links between antibody and immunological disease, with FcγRIIA promoting tissue injury and FcγRIIIB and FcγRIIA displaying specialized context-dependent functions in neutrophil recruitment.
AB - Inflammation mediated by antibody-antigen complexes contributes to autoimmune diseases. Mice deficient in the common Fcγ-chain are protected from IgG-mediated glomerulonephritis and the reverse passive Arthus (RPA) reaction and FcR-bearing macrophages, and mast cells have been assigned primary roles in these processes. Here we demonstrate that neutrophil-selective transgenic expression of the two uniquely human neutrophil Fc gamma receptors (FcγRs), FcγRIIA and FcγRIIIB, in Fcγ-chain-deficient mice restored susceptibility to progressive glomerulonephritis and the cutaneous RPA reaction. FcγRIIIB and FcγRIIA mediated neutrophil accumulation, whereas FcγRIIA alone promoted organ injury. In a model of soluble immune complexes deposited within the vasculature, FcγRIIIB was responsible for neutrophil slow rolling and adhesion whereas in the cremaster RPA, induced by both vascular and tissue soluble immune complexes, FcγRIIA predominated. Thus, human FcγRs on neutrophils serve as molecular links between antibody and immunological disease, with FcγRIIA promoting tissue injury and FcγRIIIB and FcγRIIA displaying specialized context-dependent functions in neutrophil recruitment.
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U2 - 10.1016/j.immuni.2008.04.013
DO - 10.1016/j.immuni.2008.04.013
M3 - Article
C2 - 18538590
AN - SCOPUS:44649123547
SN - 1074-7613
VL - 28
SP - 833
EP - 846
JO - Immunity
JF - Immunity
IS - 6
ER -
