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Fcgamma receptors modulate pulmonary inflammation by activating innate immune cells in murine hypersensitivity pneumonitis.

Park HJ, Kim HS, Chung DH - Immune Netw (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus

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).
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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).

Mentions: Many studies have indicated that various cytokines and chemokines are important in the pathogenesis of inflammatory lung diseases (8,10,26,27). Cytokines and chemokines induced by administration of SR antigen mediate the recruitment of immune cells and induce differentiation of Th1 cells, resulting in granuloma formation. To evaluate cytokines and chemokines expression in FcγR-/- and B6 mice after SR antigen administration, we measured mRNAs of IFN-γ, IL-4, IP-10, Mip1α, RANTES, and MCP-1 in the lungs. The expression of IP-10, Mip1α, RANTES, and MCP-1 was reduced in FcγR-/- mice compared to B6 mice (Fig. 3A). Among these chemokines, the production of IP-10 was significantly different between B6 and FcγR-/- mice. Upon inoculation of SR-antigen, FcγR-/- mice exhibited the low levels of IFN-γ, whereas the transcript level of IL-4 was significantly increased (Fig. 3B). Therefore, FcγR-/- mice show decreased chemokines expression and Th2-dominant immune responses during SR-induced HP.


Fcgamma receptors modulate pulmonary inflammation by activating innate immune cells in murine hypersensitivity pneumonitis.

Park HJ, Kim HS, Chung DH - Immune Netw (2010)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2837154&req=5

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).
Mentions: Many studies have indicated that various cytokines and chemokines are important in the pathogenesis of inflammatory lung diseases (8,10,26,27). Cytokines and chemokines induced by administration of SR antigen mediate the recruitment of immune cells and induce differentiation of Th1 cells, resulting in granuloma formation. To evaluate cytokines and chemokines expression in FcγR-/- and B6 mice after SR antigen administration, we measured mRNAs of IFN-γ, IL-4, IP-10, Mip1α, RANTES, and MCP-1 in the lungs. The expression of IP-10, Mip1α, RANTES, and MCP-1 was reduced in FcγR-/- mice compared to B6 mice (Fig. 3A). Among these chemokines, the production of IP-10 was significantly different between B6 and FcγR-/- mice. Upon inoculation of SR-antigen, FcγR-/- mice exhibited the low levels of IFN-γ, whereas the transcript level of IL-4 was significantly increased (Fig. 3B). Therefore, FcγR-/- mice show decreased chemokines expression and Th2-dominant immune responses during SR-induced HP.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.

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.

No MeSH data available.


Related in: MedlinePlus