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PMID: 18538590 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Human neutrophil Fcgamma receptors initiate and play specialized nonredundant roles in antibody-mediated inflammatory diseases.

Immunity ·Vol. 28 ·No. 6 ·2008-06-00 ·Pages 833-46

Tsuboi N, Asano K, Lauterbach M, Mayadas TN

Abstract

Inflammation mediated by antibody-antigen complexes contributes to autoimmune diseases. Mice deficient in the common Fcgamma-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 (FcgammaRs), FcgammaRIIA and FcgammaRIIIB, in Fcgamma-chain-deficient mice restored susceptibility to progressive glomerulonephritis and the cutaneous RPA reaction. FcgammaRIIIB and FcgammaRIIA mediated neutrophil accumulation, whereas FcgammaRIIA alone promoted organ injury. In a model of soluble immune complexes deposited within the vasculature, FcgammaRIIIB was responsible for neutrophil slow rolling and adhesion whereas in the cremaster RPA, induced by both vascular and tissue soluble immune complexes, FcgammaRIIA predominated. Thus, human FcgammaRs on neutrophils serve as molecular links between antibody and immunological disease, with FcgammaRIIA promoting tissue injury and FcgammaRIIIB and FcgammaRIIA displaying specialized context-dependent functions in neutrophil recruitment.

MeSH Terms
Animals Antibodies/immunology Antigen-Antibody Complex/immunology,metabolism Antigens, CD/immunology,metabolism Arthus Reaction/immunology,metabolism Cell Adhesion Glomerulonephritis/immunology,metabolism Humans Inflammation/immunology,metabolism Leukocyte Rolling Mice Mice, Transgenic Neutrophils/immunology,metabolism Reactive Oxygen Species/metabolism Receptors, IgG/immunology,metabolism
Chemicals
Antibodies Antigen-Antibody Complex Antigens, CD Fc gamma receptor IIA Reactive Oxygen Species Receptors, IgG
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Tsuboi Naotake
Center of Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Asano Kenichi
Lauterbach Michael
Mayadas Tanya N
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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2008.04.013
Published
2008-06-00
Pages
833-46
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC2577844
Subset
IM
Grants
NHLBI NIH HHS · R01 HL065095-09 · United States
NIAMS NIH HHS · AR050800 · United States
NHLBI NIH HHS · R01 HL065095 · United States
NIAMS NIH HHS · R01 AR050800 · United States
NIAMS NIH HHS · R01 AR050800-04 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2008.04.013 PMC Full Text View journal details
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