Pregnancy exacerbates neutrophil responses in murine lungs after cigarette smoke exposure

Exposure to environmental smoke during pregnancy has detrimental effects on maternal health and contributes to the development of severe respiratory diseases. Pregnant mice were subjected to either whole-body smoke or air exposure throughout pregnancy and lactation. 24 h after the final smoke exposure, BALF cell counts and the level of calprotectin in BLAF, serum, and feces were investigated. Pregnant mice exhibited significantly higher calprotectin levels and neutrophil influx in BALF compared to their non-pregnant counterparts. Interestingly, in both pregnant and non-pregnant mice exposed to CS, significantly elevated levels of neutrophils and calprotectin were observed compared to those exposed to air. These findings are further underscored by RNA sequencing results of the lung tissues, as CS-exposed dams, particularly during pregnancy, showed elevated expression of inflammatory genes associated with neutrophil function and migration. Similarly, in air-exposed mice, pregnancy resulted in a significant increase in serum calprotectin levels compared to non-pregnant groups, while surprisingly, this increase was suppressed in pregnant mice exposed to CS. In contrast, no significant differences in calprotectin levels were observed in fecal samples. In summary, there are distinct effects of CS on neutrophil numbers and calprotectin levels in pregnant and non-pregnant mice, in BALF and serum. These findings highlight the impact of pregnancy-induced changes in the immune system especially on the migration and activation of neutrophils. They further show that pregnancy exacerbates neutrophil inflammatory responses towards environmental noxious triggers.