Journal
CLINICAL IMMUNOLOGY
Volume 110, Issue 2, Pages 172-180Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2003.11.007
Keywords
mast cell; Fc receptor; degranulation; cytokine; IgG; C3a; taqman; beta-hexosaminidase
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Human mast cells (huMC) increase surface expression of FcgammaRI (CD64) in response to IFNgamma. Subsequent receptor aggregation of FcgammaRI using CD64-specific F(ab')(2) or antibody directed against FcgammaRI-bound IgG results in cell activation. Human mast cells may be observed degranulating in inflammation associated with autoimmune disease and where IFNgamma is produced. We sought to determine if human mast cells cultured in IFNgamma would degranulate in response to aggregated IgG, what mediators might be generated (i.e., cytokines and eicosanoids), and whether C3a might enhance such activation. Activation of IFNgamma-treated huMC sensitized with 1 mug/ml aggregated IgG(1) resulted in 15-30% degranulation (beta-hexosaminidase release), which was half-maximal by 7.5 min; no degranulation was observed using heat-generated aggregates of IgG(2), IgG(3), or IgG(4). Activation using aggregated IgG(1) led to PGD(2) and LTC4 generation as well as enhanced IL-3, IL-13, GM-CSF, and TNFalpha production. Preincubation of cells with F(ab')(2) from CD64-specific clone 10.1 reduced aggregated IgG(1)-mediated beta-hexosaminidase release by 38% while degranulation was unaffected by blocking FcgammaRII with F(ab')(2)-specific antibody (clone 7.3). Simultaneous activation of huMC via aggregated IgG and C3a led to additive degranulation. These data support a mechanism by which mast cells may contribute to the inflammatory component in fibrosis, vasculitis, and arthritis. (C) 2003 Elsevier Inc. All rights reserved.
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