Critical role of the Fc receptor gamma-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation.
The FcR common gamma-chain (FcRgamma) is an essential component of the receptors FcepsilonRI, FcgammaRI, and FcgammaRIII, which are expressed on many inflammatory cell types. The role of these receptors in the initiation or maintenance of allergic inflammation has not been well defined. FcRgamma-deficient (FcRgamma(-/-)) and control (wild-type (WT)) mice were sensitized and subsequently challenged with OVA. Following sensitization and challenge to OVA, FcRgamma-deficient (FcRgamma(-/-)) mice developed comparable levels of IgE and IgG1 as WT mice. However, numbers of eosinophils, levels of IL-5, IL-13, and eotaxin in bronchoalveolar lavage fluid, and mononuclear cell (MNC) proliferative responses to OVA were significantly reduced, as was airway hyperresponsiveness (AHR) to inhaled methacholine. Reconstitution of FcRgamma(-/-) mice with whole spleen MNC from WT mice before sensitization restored development of AHR and the numbers of eosinophils in bronchoalveolar lavage fluid; reconstitution after sensitization but before OVA challenge only partially restored these responses. These responses were also restored when FcRgamma(-/-) mice received T cell-depleted MNC, T and B cell-depleted MNC, or bone marrow-derived dendritic cells before sensitization from FcR(+/+) or FcgammaRIII-deficient but not FcRgamma(-/-) mice. The expression levels of FcgammaRIV on bone marrow-derived dendritic cells from FcR(+/+) mice were found to be low. These results demonstrate that expression of FcRgamma, most likely FcgammaRI, on APCs is important during the sensitization phase for the development of allergic airway inflammation and AHR.
Kitamura
Kenichi
K
Department of Medicine II, Faculty of Medicine, Okayama University Medical School, Okayama, Japan.
Takeda
Katsuyuki
K
Koya
Toshiyuki
T
Miyahara
Nobuaki
N
Kodama
Taku
T
Dakhama
Azzeddine
A
Takai
Toshiyuki
T
Hirano
Atsushi
A
Tanimoto
Mitsune
M
Harada
Mine
M
Gelfand
Erwin W
EW
D000485:Allergens / Q000276:immunology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis; D016207:Cytokines / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008214:Lymphocytes / Q000276:immunology; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008817:Mice, Mutant Strains; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000473:pathology; D017452:Receptors, IgG / Q000235:genetics / Q000502:physiology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D000485:Allergens; D016085:Bronchoconstrictor Agents; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; C485701:Fcgr1 protein, mouse; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG; D016210:Methacholine Chloride; D007073:Immunoglobulin E; D010047:Ovalbumin