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
Sex and SP-A2 Dependent NAD(H) Redox Alterations in Mouse Alveolar Macrophages in Response to Ozone Exposure: Potential Implications for COVID-19