Article ; Online: Delivery of GM-CSF to Protect against Influenza Pneumonia.
PloS one
2015 Volume 10, Issue 4, Page(s) e0124593
Abstract: ... viruses. Recent studies have highlighted the importance of innate immunity in protecting against influenza ... Conclusion: We also demonstrate that protection is species specific and human GM-CSF do not protect the mice ... we report that pulmonary delivery of GM-CSF to wild type young and aged mice abrogated mortality from IAV ...
| 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. |
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| MeSH term(s) | Animals ; Cell Proliferation/drug effects ; Cytokines/metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology ; Humans ; Influenza A Virus, H1N1 Subtype/pathogenicity ; Intercellular Signaling Peptides and Proteins/metabolism ; Lung/diagnostic imaging ; Lung/metabolism ; Lung/virology ; Macrophages, Alveolar/cytology ; Macrophages, Alveolar/drug effects ; Macrophages, Alveolar/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic ; Orthomyxoviridae Infections/drug therapy ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/virology ; Phagocytosis/drug effects ; Pneumonia/prevention & control ; Protective Agents/pharmacology ; Protective Agents/therapeutic use ; Quantum Dots/chemistry ; Quantum Dots/metabolism ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/genetics ; Recombinant Proteins/pharmacology ; Tomography, X-Ray Computed |
| Chemical Substances | Cytokines ; Intercellular Signaling Peptides and Proteins ; Protective Agents ; Recombinant Proteins ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1) |
| Language | English |
| Publishing date | 2015 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 1932-6203 |
| ISSN (online) | 1932-6203 |
| DOI | 10.1371/journal.pone.0124593 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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