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Delivery of GM-CSF to Protect against Influenza Pneumonia.

Subramaniam R, Hillberry Z, Chen H, Feng Y, Fletcher K, Neuenschwander P, Shams H - PLoS ONE (2015)

Bottom Line: Granulocyte-macrophage colony stimulating factor (GM-CSF) contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production.Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM).We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection.

View Article: PubMed Central - PubMed

Affiliation: Center for Pulmonary and Infectious Diseases Control (CPIDC), The University of Texas Health Science Center at Tyler, 11937 U.S. Highway 271, Tyler, TX, United States of America.

ABSTRACT

Background: Since adaptive immunity is thought to be central to immunity against influenza A virus (IAV) pneumonias, preventive strategies have focused primarily on vaccines. However, vaccine efficacy has been variable, in part because of antigenic shift and drift in circulating influenza viruses. Recent studies have highlighted the importance of innate immunity in protecting against influenza.

Methods: Granulocyte-macrophage colony stimulating factor (GM-CSF) contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production.

Results: Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM). In this study, we report that pulmonary delivery of GM-CSF to wild type young and aged mice abrogated mortality from IAV.

Conclusion: We also demonstrate that protection is species specific and human GM-CSF do not protect the mice nor stimulates mouse immunity. We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection.

No MeSH data available.


Related in: MedlinePlus

Effects of GM-CSF on alveolar macrophages, lung cytokines and growth factor.Wild type C57Bl/6 mice were treated intranasally daily with murine GM-CSF (mGM-CSF) or human GM-CSF (hGM-CSF) for 7 days. On day 8, mice were sacrificed and the number of alveolar macrophages in BAL (A), levels of TNFα (B), MCP-1 (C), amphiregulin (D) and expression of PU.1 (E) in the BAL/lungs were measured. Depicted data show mean of 3–5 animals per group ±SEM and a representative of two independent experiments. *p<0.01, **p<0.001, ***p<0.0001.
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pone.0124593.g002: Effects of GM-CSF on alveolar macrophages, lung cytokines and growth factor.Wild type C57Bl/6 mice were treated intranasally daily with murine GM-CSF (mGM-CSF) or human GM-CSF (hGM-CSF) for 7 days. On day 8, mice were sacrificed and the number of alveolar macrophages in BAL (A), levels of TNFα (B), MCP-1 (C), amphiregulin (D) and expression of PU.1 (E) in the BAL/lungs were measured. Depicted data show mean of 3–5 animals per group ±SEM and a representative of two independent experiments. *p<0.01, **p<0.001, ***p<0.0001.

Mentions: Next we evaluated the effects of mGM-CSF and hGM-CSF on total cell counts of bronchoalveolar lavage (BAL) that were over 95% alveolar macrophages and an indicator of in vivo immune cell proliferation in the alveolar space. Overexpression of mGM-CSF in the lungs in mice significantly increases the numbers of alveolar macrophages [7]. Wild type C57BL/6 mice were treated with either mGM-CSF, hGM-CSF or PBS intranasally daily for seven days (1.34 μg/g body weight). On day eight, mice were sacrificed and their lungs were lavaged. Mice treated with PBS and hGM-CSF had comparable number of AMs in their BAL whereas mGM-CSF-treated mice showed markedly increased number of AM and had approximately 27 times more AM than PBS- and hGM-CSF-treated mice (Fig 2A, P<0.0001).


Delivery of GM-CSF to Protect against Influenza Pneumonia.

Subramaniam R, Hillberry Z, Chen H, Feng Y, Fletcher K, Neuenschwander P, Shams H - PLoS ONE (2015)

Effects of GM-CSF on alveolar macrophages, lung cytokines and growth factor.Wild type C57Bl/6 mice were treated intranasally daily with murine GM-CSF (mGM-CSF) or human GM-CSF (hGM-CSF) for 7 days. On day 8, mice were sacrificed and the number of alveolar macrophages in BAL (A), levels of TNFα (B), MCP-1 (C), amphiregulin (D) and expression of PU.1 (E) in the BAL/lungs were measured. Depicted data show mean of 3–5 animals per group ±SEM and a representative of two independent experiments. *p<0.01, **p<0.001, ***p<0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414562&req=5

pone.0124593.g002: Effects of GM-CSF on alveolar macrophages, lung cytokines and growth factor.Wild type C57Bl/6 mice were treated intranasally daily with murine GM-CSF (mGM-CSF) or human GM-CSF (hGM-CSF) for 7 days. On day 8, mice were sacrificed and the number of alveolar macrophages in BAL (A), levels of TNFα (B), MCP-1 (C), amphiregulin (D) and expression of PU.1 (E) in the BAL/lungs were measured. Depicted data show mean of 3–5 animals per group ±SEM and a representative of two independent experiments. *p<0.01, **p<0.001, ***p<0.0001.
Mentions: Next we evaluated the effects of mGM-CSF and hGM-CSF on total cell counts of bronchoalveolar lavage (BAL) that were over 95% alveolar macrophages and an indicator of in vivo immune cell proliferation in the alveolar space. Overexpression of mGM-CSF in the lungs in mice significantly increases the numbers of alveolar macrophages [7]. Wild type C57BL/6 mice were treated with either mGM-CSF, hGM-CSF or PBS intranasally daily for seven days (1.34 μg/g body weight). On day eight, mice were sacrificed and their lungs were lavaged. Mice treated with PBS and hGM-CSF had comparable number of AMs in their BAL whereas mGM-CSF-treated mice showed markedly increased number of AM and had approximately 27 times more AM than PBS- and hGM-CSF-treated mice (Fig 2A, P<0.0001).

Bottom Line: Granulocyte-macrophage colony stimulating factor (GM-CSF) contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production.Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM).We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection.

View Article: PubMed Central - PubMed

Affiliation: Center for Pulmonary and Infectious Diseases Control (CPIDC), The University of Texas Health Science Center at Tyler, 11937 U.S. Highway 271, Tyler, TX, United States of America.

ABSTRACT

Background: Since adaptive immunity is thought to be central to immunity against influenza A virus (IAV) pneumonias, preventive strategies have focused primarily on vaccines. However, vaccine efficacy has been variable, in part because of antigenic shift and drift in circulating influenza viruses. Recent studies have highlighted the importance of innate immunity in protecting against influenza.

Methods: Granulocyte-macrophage colony stimulating factor (GM-CSF) contributes to maturation of mononuclear phagocytes, enhancing their capacity for phagocytosis and cytokine production.

Results: Overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) in the lung of transgenic mice provides remarkable protection against IAV, which depends on alveolar macrophages (AM). In this study, we report that pulmonary delivery of GM-CSF to wild type young and aged mice abrogated mortality from IAV.

Conclusion: We also demonstrate that protection is species specific and human GM-CSF do not protect the mice nor stimulates mouse immunity. We also show that IAV-induced lung injury is the culprit for side-effects of GM-CSF in treating mice after IAV infection, and introduce a novel strategy to deliver the GM-CSF to and retain it in the alveolar space even after IAV infection.

No MeSH data available.


Related in: MedlinePlus