Sex-dependent NAD(H) redox alteration in alveolar macrophages from mice expressing SP-A2 (but not from SP-A KO) in response to ozone exposure: Potential implications for COVID-19

He N. Xu, Zhenwu Lin, Chintan K. Gandhi, Shaili Amatya, Yunhua Wang, Lin Z. Li, Joanna Floros

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Co-enzyme nicotinamide adenine dinucleotide (NAD(H)) redox plays a key role in macrophage function. Surfactant protein (SP-) A modulates the functions of alveolar macrophages (AM) and ozone (O3) exposure in the presence or absence of SP-A and reduces mouse survival in a sex-dependent manner. It is unclear whether and how NAD(H) redox status plays a role in the innate immune response in a sex-dependent manner. We investigated the NAD(H) redox status of AM from SP-A2 and SP-A knockout (KO) mice in response to O3 or filtered air (control) exposure using optical redox imaging technique. We found: (i) In SP-A2 mice, the redox alteration of AM in response to O3 showed sex-dependence with AM from males being significantly more oxidized and having a higher level of mitochondrial reactive oxygen species than females; (ii) AM from KO mice were more oxidized after O3 exposure and showed no sex differences; (iii) AM from female KO mice were more oxidized than female SP-A2 mice; and (iv) Two distinct subpopulations characterized by size and redox status were observed in a mouse AM sample. In conclusions, the NAD(H) redox balance in AM responds to O3 in a sex-dependent manner and the innate immune molecule, SP-A2, contributes to this observed sex-specific redox response.

Original languageEnglish (US)
Article number915
Pages (from-to)1-19
Number of pages19
JournalAntioxidants
Volume9
Issue number10
DOIs
StatePublished - Oct 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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