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GM-CSF in the Lung Protects Against Lethal Influenza Infection.

Authors: Huang, FF  Barnes, PF  Feng, Y  Donis, R  Chroneos, ZC  Idell, S  Allen, T  Perez, DR  Whitsett, JA  Dunussi-Joannopoulos, K  Shams, H 
Citation: Huang FF, etal., Am J Respir Crit Care Med. 2011 Apr 7.
Pubmed: (View Article at PubMed) PMID:21474645
DOI: Full-text: DOI:10.1164/rccm.201012-2036OC

RATIONALE: Alveolar macrophages contribute to host defenses against influenza in animal models. Enhancing alveolar macrophage function may contribute to protection against influenza OBJECTIVE: To determine if increased expression of granulocyte-macrophage colony stimulating factor in the lung increases resistance to influenza METHODS: Wild-type mice and transgenic mice that expressed granulocyte macrophage-colony stimulating factor in the lung were infected with influenza virus, and lung pathology, weight loss and mortality were measured. We also administered granulocyte-macrophage colony stimulating factor to the lungs of wild-type mice that were infected with influenza virus. MEASUREMENTS AND MAIN RESULTS: Wild-type mice all died after infection with different strains of influenza virus, but all transgenic mice expressing granulocyte-macrophage colony stimulating factor in the lungs survived. The latter also had greatly reduced weight loss and lung injury, and showed histologic evidence of a rapid host inflammatory response that controlled infection. The resistance of transgenic mice to influenza was abrogated by elimination of alveolar phagocytes, but not by depletion of T-cells, B-cells or neutrophils. Transgenic mice had far more alveolar macrophages than wild-type mice, and they were more resistant to influenza-induced apoptosis. Delivery of intranasal granulocyte macrophage-colony stimulating factor to wild-type mice also conferred resistance to influenza. CONCLUSIONS: Granulocyte-macrophage colony stimulating factor confers resistance to influenza by enhancing innate immune mechanisms that depend on alveolar macrophages. Pulmonary delivery of this cytokine has the potential to reduce the morbidity and mortality due to influenza virus.

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RGD Object Information
RGD ID: 5131470
Created: 2011-04-28
Species: All species
Last Modified: 2011-04-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.