Journal
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
Volume 111, Issue 10, Pages 707-714Publisher
OXFORD UNIV PRESS
DOI: 10.1093/qjmed/hcy160
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Funding
- General Program of NSFC [81470269]
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2016YFC1200400]
- Major Research Plan of NSFC [91542105]
- Key Program of NSFC [81730001]
- Strategic Leading Project (B) of CAS [XDPB0303]
- International Collaboration project of CAS [GJHZ1880]
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Background: Deficiency of hypoxia-induced factor-1 alpha (HIF-1 alpha) in macrophages reduced lipopolysaccharide (LPS)-induced mortality; however, whether HIF-1 alpha expression in myeloid cells would contribute to the development of Escherichia coli (E. coil) or LPS-induced acute lung injury (ALI) is less investigated. Aim: To test whether deletion of Hif1 alpha in myeloid cells affects E. coil or LPS-induced ALI and to elicit the underlying mechanisms. Design: Laboratory study. Methods: We intratracheally challenged Hif1 alpha(fl/fl) and Hif1 alpha(fl/fl)LysM(Cre) mice with E. coli or LPS to analyze lung and spleen inflammatory responses. Flow cytometry was used to analyze the changes of alpha 7 nAChR(+)CD11b(+) cells in the lung and spleen. Double knockout of Chma7 and Itgam mice were used to examine expression of HIF-1 alpha during E. coli lung infection. Vagotomy was performed to demonstrate the role of vagus nerve in mediating protective effects of deletion of Hif1 alpha in myeloid cells on LPS-induced ALI. Results: Deletion of Hif1 alpha in myeloid cells could reduce lung edema, inflammatory cell infiltration, and lung and BAL inflammatory cytokines in E. coli-induced ALI. Flow cytometric analysis revealed that alpha 7 nAChR(+)CD11b(+) cells in the lung and spleen were markedly increased in E. coil-challenged Hif1 alpha(fl/fl)LYsM(Cre)mice compared with E. coil-challenged Hif1 alpha(fl/fl)LYsM(Cre) mice. Double knockout of Chrna7 and Itgam increased HIF-1 alpha expression in lung and spleen cells during lung E. coli infection. Vagotomy abolished the protective effect of deletion of Hipa in myeloid cells on LPS-induced ALI. Conclusion: Deletion of Hif1 alpha in myeloid cells could protect mice from lung injury depending on alpha 7 nAChR(+)CD11b(+) cells and innervation of vagal circuits.
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