Am. J. Respir. Cell Mol. Biol., Volume 26, Number 1, January, 2002 31-41

Maternal Nicotine Exposure Upregulates Collagen Gene Expression in Fetal Monkey Lung
Association with 7 Nicotinic Acetylcholine Receptors

Harmanjatinder S. Sekhon, Jennifer A. Keller, Becky J. Proskocil, Ellen L. Martin, and Eliot R. Spindel

Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton, Oregon; and Department of Pathology, Oregon Health Sciences University, Portland, Oregon

The recent identification of nicotinic acetylcholine receptors (nAChR) in pulmonary fibroblasts suggests that in utero nicotine exposure may alter collagen expression by these cells in the developing lung. To test this hypothesis, timed-pregnant rhesus monkeys were administered nicotine (1-1.5 mg/kg/d, subcutaneously) using osmotic minipumps from Days 26-134 or 26-160 of gestation (term = 165 d). In utero nicotine exposure significantly increased airway wall area per unit epithelial basement membrane. Collagen type I and III mRNA expression and immunostaining were significantly increased in the airway and alveolar walls of the nicotine-treated group. Elastin mRNA expression increased, but protein expression in parenchyma remained unchanged. Dual labeling studies colocalized 7 nAChR and collagen to the same cells in airway wall cells, and colocalization of 7 nAChR and collagen was confirmed in isolated pulmonary fibroblasts. These findings suggest that nicotine may directly interact with 7 nAChR to increase collagen accumulation in airway and alveolar walls following in utero nicotine exposure. These data suggest that passage of nicotine across the placenta to increase collagen deposition and therefore increase airway wall dimensions in fetal lung may partially explain the observed alterations in lung mechanics in the infants of mothers who smoke during pregnancy.

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