Cigarette smoke exposure during pregnancy alters fetomaternal cell trafficking leading to retention of microchimeric cells in the maternal lung.

Anja Vogelgesang,Anna Blumental Perry,Caroline Barone,Elaine Tam,Cristina Scapin,Christiane E L Dammann,Colette Kanellopoulos-Langevin

doi:10.1371/journal.pone.0088285

Abstract

Cigarette smoke exposure causes chronic oxidative lung damage. During pregnancy, fetal microchimeric cells traffic to the mother. Their numbers are increased at the site of acute injury. We hypothesized that milder chronic diffuse smoke injury would attract fetal cells to maternal lungs. We used a green-fluorescent-protein (GFP) mouse model to study the effects of cigarette smoke exposure on fetomaternal cell trafficking. Wild-type female mice were exposed to cigarette smoke for about 4 weeks and bred with homozygote GFP males. Cigarette smoke exposure continued until lungs were harvested and analyzed. Exposure to cigarette smoke led to macrophage accumulation in the maternal lung and significantly lower fetal weights. Cigarette smoke exposure influenced fetomaternal cell trafficking. It was associated with retention of GFP-positive fetal cells in the maternal lung and a significant reduction of fetal cells in maternal livers at gestational day 18, when fetomaternal cell trafficking peaks in the mouse model. Cells quickly clear postpartum, leaving only a few, difficult to detect, persisting microchimeric cells behind. In our study, we confirmed the postpartum clearance of cells in the maternal lungs, with no significant difference in both groups. We conclude that in the mouse model, cigarette smoke exposure during pregnancy leads to a retention of fetal microchimeric cells in the maternal lung, the site of injury. Further studies will be needed to elucidate the effect of cigarette smoke exposure on the phenotypic characteristics and function of these fetal microchimeric cells, and confirm its course in cigarette smoke exposure in humans.

Highlights

Each year, more than 443,000 Americans die of tobacco-related illnesses such as chronic obstructive pulmonary disease (COPD) and lung cancer [1]
We evaluated macrophage recruitment in parasagittal lung sections obtained from smoker and control animals about 6 weeks after starting the Cigarette smoke (CS) exposure, using immunohistochemistry staining for Mac3, an antigen expressed in macrophages (Figure 2A)
There were no further differences in the macrophage numbers between pregnant and non-pregnant smokers indicating that the duration of CS exposure or of the presence of fetal microchimeric cells was too short to see a significant impact on macrophage numbers

Summary

Introduction

More than 443,000 Americans die of tobacco-related illnesses such as chronic obstructive pulmonary disease (COPD) and lung cancer [1]. These illnesses cause more deaths in women than breast cancer does. Smoking during pregnancy is still a widespread problem. About 14% of women in the United States state that they are smoking during pregnancy [2]. CS exposure during pregnancy is associated with preterm delivery, low birth weight, and an increased morbidity in the newborn [4]. Animal studies have shown that fetal nicotine exposure may affect the development of the lungs and multiple other organs, and cause long-lasting effects on body adiposity and endocrine function [5]

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Results

Conclusion