Prenatal Exposure to Nicotine and Childhood Asthma: Role of Nicotine Acetylcholine Receptors, Neuropeptides and Fibronectin Expression in Lung
Abstract
Asthma is a chronic lung disease characterized by airway dysfunction. Of the many factors implicated in the pathogenesis of asthma, a strong association exists between prenatal and postnatal exposure to environmental tobacco smoke (ETS). This is particularly true in infancy and in childhood where ETS exposure is associated with a higher incidence or prevalence of asthma, and with measures of decreased flow in the airways, bronchial hyperresponsiveness, and increased respiratory infections. It has been speculated that the relationship between ETS and asthma is secondary to reduced airway flow caused by tobacco-induced prenatal alterations in airway architecture and/or bronchial reactivity. However, the exact mechanisms by which prenatal ETS promotes airway dysfunction in children remain unelucidated. The authors hypothesize that prenatal exposure to nicotine, a major component of tobacco that transverses the placenta, is largely responsible for the development of asthma in children born of mothers who smoke. Specifically, they hypothesize that nicotine is recognized by specific cellular proteins called nicotinic acetylcholine receptors (nAChRs) that are expressed by lung cells termed fibroblasts and pulmonary neuroendocrine cells (PNEC). In fibroblasts, this interaction triggers the exaggerated expression of a connective tissue protein called fibronectin. In PNECs, nicotine stimulates cell growth and the excessive secretion of neuropeptides that affect airway formation and lung growth, and that stimulate smooth muscle cells to contract. In this fashion, nicotine can affect airway development and promote disease during childhood. This proposal will test the hypothesis in animal models of lung development and hyperreactive airways.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2006
- Accession Number
- ADA467902
Entities
People
- Jesse Roman
Organizations
- Emory University