Immune Netw.  2010 Feb;10(1):26-34. 10.4110/in.2010.10.1.26.

Fcgamma Receptors Modulate Pulmonary Inflammation by Activating Innate Immune Cells in Murine Hypersensitivity Pneumonitis

• Park HJ
• Kim HS
• Chung DH

• KMID: 1456194
• DOI: http://doi.org/10.4110/in.2010.10.1.26

Abstract

BACKGROUND
Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. The family of Fcgamma receptors (FcgammaRs) has emerged as central regulators for modulating both pro-and anti-inflammatory responses. However, the role of FcgammaRs in the development of HP has not been investigated yet. METHODS: To explore the functional roles of FcgammaRs in HP, FcgammaR-/- and B6 mice were challenged with Saccharopolyspora rectivirgula (SR) antigen intranasally, and compared these mice in terms of the histological change, infiltrated immune cells in BALF and in vitro immune responses. RESULTS: FcgammaR-/- mice exhibited attenuation of HP in terms of histological alterations, and reduced numbers of neutrophils and macrophages in and the increased CD4:CD8 ratio of bronchoalveolar lavage fluid. The lungs of FcgammaR-/- mice showed high production of Th2 cytokine such as IL-4 and slightly low production of Th1 cytokine, INF-gamma compared to those of B6 mice. However, SR-specific adaptive immune responses of FcgammaR-/- mice were similar to those of B6 mice. CONCLUSION: These results demonstrate that activating Fcgamma receptors play an important role in activating neutrophils and macrophages in pulmonary inflammation and inducing Th1 differentiation by regulating cytokine expression in SR-induced HP.

Keyword

Fcgamma receptors; Innate immunity; Hypersensitivity pneumonitis

MeSH Terms

Alveolitis, Extrinsic Allergic
Animals
Bronchoalveolar Lavage Fluid
Humans
Hypersensitivity
Immunity, Innate
Interleukin-4
Lung
Lung Diseases, Interstitial
Macrophages
Mice
Neutrophils
Pneumonia
Saccharopolyspora
Interleukin-4

Figure

• 

  Figure 1 B6 and FcγR-/- mice show different cellular composition of BALF during SR-induced HP. BALF cells were obtained from mice 7 days after the first inoculation with SR antigen and counted. The cellular subset was evaluated using flow cytometric analysis. (A) FSC and SSC scatter diagrams of total BALF cells in B6 and FcγR-/- mice (B, C) The numbers of immune cells in BALF were counted and (D) the percentages of CD4+ and CD8+ T cells were determined among the gated lymphocytes in flow cytometric analysis. The results shown are representative of three independent experiments and statistical analysis was performed using the program Prism 4.0 (n=3, N.S.: not significant, *p<0.05, **p<0.01, B6 mice versus FcγR-/- mice).

• 

  Figure 2 Hypersensitivity pneumonitis is attenuated in FcγR-/- mice compared to B6 mice in terms of histological alteration. In B6 and FcγR-/- mice, hypersensitivity pneumonitis was induced by inoculating SR antigen intranasally. These mice were sacrificed 3 weeks after HP induction. (A) The lungs were removed from the B6 and FcγR-/- mice, and paraffin sections were stained with H&E. Original magnification, ×100 or ×400. The photographs are representative of the three mice in each group. (B) Inflammatory responses in the lungs of B6 and FcγR-/- mice were graded. 0 (n=3, *p<0.05, B6 mice versus FcγR-/- mice).

• 

  Figure 3 FcγR-/- mice alter chemokines and cytokines expression in the lungs during SR-induced HP. The transcription of chemokines such as IP-10, Mip-1α, RANTES and MCP-1 (A) and cytokines, IFN-γ, and IL-4 (B) were measured using real-time PCR in the lungs from B6 and FcγR-/- mice 7 days after the first administration of SR antigen. All expression levels were normalized to GAPDH. The results shown are representative of three independent experiments and statistical analysis was performed using the program Prism 4.0 (n=3, *p<0.05, B6 mice versus FcγR-/- mice).

• 

  Figure 4 FcγR-/- mice show similar SR-specific proliferation of immune cells and production of IgG during SR-induced HP. HP was induced by intranasal inoculation of SR antigen. (A, B) The lungs were removed from the B6 and FcγR-/- mice 3 weeks after induction of HP, and the amounts of SR-specific IgG in BALF and serum were measured 3 weeks after HP induction using ELISA. (C) Immune cell proliferation to SR antigen was evaluated by a MTS assay using spleen cells 21 days after the first nasal inoculation with SR antigen. The results shown are representative of three independent experiments and statistical analysis was performed using the program Prism 4.0 (n=3, N.S.: not significant,, B6 mice versus FcγR-/- mice).

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