Critical role of the Fc receptor gamma-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation.

Abstract

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.

• Authors: Kenichi Kitamura, Katsuyuki Takeda, Toshiyuki Koya, Nobuaki Miyahara, Taku Kodama, Azzeddine Dakhama, Toshiyuki Takai, Atsushi Hirano, Mitsune Tanimoto, Mine Harada, Erwin W Gelfand
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 178 Issue 1 Pg. 480-8 (Jan 01 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17182587 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Allergens
• Bronchoconstrictor Agents
• Ccl11 protein, mouse
• Chemokine CCL11
• Chemokines, CC
• Cytokines
• Fcgr1 protein, mouse
• Fcgr3 protein, mouse
• Immunoglobulin G
• Receptors, IgG
• Methacholine Chloride
• Immunoglobulin E
• Ovalbumin

Topics

• Allergens (immunology)
• Animals
• Bronchial Hyperreactivity (immunology)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• Bronchoconstrictor Agents (administration & dosage)
• Chemokine CCL11
• Chemokines, CC (analysis)
• Cytokines (analysis)
• Dendritic Cells (immunology)
• Eosinophils (immunology)
• Immunoglobulin E (blood)
• Immunoglobulin G (blood)
• Lymphocytes (immunology)
• Methacholine Chloride (administration & dosage)
• Mice
• Mice, Mutant Strains
• Ovalbumin (immunology)
• Pneumonia (immunology, pathology)
• Receptors, IgG (genetics, physiology)
• Respiratory Hypersensitivity (genetics, immunology, pathology)