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Deficiency of HIF-1α in myeloid cells protects Escherichia coli or LPS-induced acute lung injury.
- Source :
-
QJM: An International Journal of Medicine . Oct2018, Vol. 111 Issue 10, p707-714. 8p. - Publication Year :
- 2018
-
Abstract
- Background Deficiency of hypoxia-induced factor-1α (HIF-1α) in macrophages reduced lipopolysaccharide (LPS)-induced mortality; however, whether HIF-1α expression in myeloid cells would contribute to the development of Escherichia coli (E. coli) or LPS-induced acute lung injury (ALI) is less investigated. Aim To test whether deletion of Hif1α in myeloid cells affects E. coli or LPS-induced ALI and to elicit the underlying mechanisms. Design Laboratory study. Methods We intratracheally challenged Hif1αfl/fl and Hif1αfl/fl LysMCre mice with E. coli or LPS to analyze lung and spleen inflammatory responses. Flow cytometry was used to analyze the changes of α7 nAChR+CD11b+ cells in the lung and spleen. Double knockout of Chrna7 and Itgam mice were used to examine expression of HIF-1α during E. coli lung infection. Vagotomy was performed to demonstrate the role of vagus nerve in mediating protective effects of deletion of Hif1α in myeloid cells on LPS-induced ALI. Results Deletion of Hif1α 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 α7 nAChR+CD11b+ cells in the lung and spleen were markedly increased in E. coli -challenged Hif1αfl/fl LysMCre mice compared with E. coli -challenged Hif1αfl/fl mice. Double knockout of Chrna7 and Itgam increased HIF-1α expression in lung and spleen cells during lung E. coli infection. Vagotomy abolished the protective effect of deletion of Hif1α in myeloid cells on LPS-induced ALI. Conclusion Deletion of Hif1α in myeloid cells could protect mice from lung injury depending on α7 nAChR+CD11b+ cells and innervation of vagal circuits. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ESCHERICHIA coli
*LUNG injuries
*LIPOPOLYSACCHARIDES
*VAGOTOMY
*MACROPHAGES
Subjects
Details
- Language :
- English
- ISSN :
- 14602725
- Volume :
- 111
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- QJM: An International Journal of Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 132179728
- Full Text :
- https://doi.org/10.1093/qjmed/hcy160