Sex differences in neutrophil extracellular trap formation

Immune responses vary between men and women. The female sex is considered protective in combatting acute infections, but disadvantageous in chronic inflammatory diseases. As neutrophils play a central role in innate immunity, they may mediate the sexual dimorphism in immune responses. Neutrophils can combat invading microbes by forming neutrophil extracellular traps (NETs). We hypothesize that females release higher amounts of NETs, leading to more robust acute immune responses. To test our hypothesis, neutrophils isolated from healthy human males and females were induced to form NETs in response to various pharmacological and biological stimuli. Total DNA content was higher in neutrophils from females compared to males. Female neutrophils released decreased levels of DNA in response to the calcium ionophore A23187. PMA, LPS, ionomycin and bacteria stimulation did not result in significant sex differences. Correlating the serum levels of the sex hormones testosterone, estradiol and progesterone to NETosis levels in the above conditions revealed a negative correlation between testosterone and A23187-mediated DNA release. No correlation was detected in relation to endogenous estradiol and progesterone levels, but a combination effect has not been fully explored. Exogenous estradiol or progesterone treatment at physiological concentrations did not influence DNA release. Given the results thus far, a sex difference in NETosis was detected with A23187 treatment but not from biological stimuli in the context of healthy neutrophils.M.Sc