Published in:
Open Access
01-12-2020 | Smoking and Nicotine Detoxification | Research
Evaluation of secondhand smoke effects on CFTR function in vivo
Authors:
Lawrence W. Rasmussen, Denise Stanford, Krina Patel, S. Vamsee Raju
Published in:
Respiratory Research
|
Issue 1/2020
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Excerpt
Cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel expressed on the mucosal surface of epithelial cells lining several tissues including airways. Inherited defects in the CFTR gene cause cystic fibrosis (CF), an autosomal recessive disease causing a progressive decline in lung function ultimately resulting in reduced life span. CF patients exhibit impaired mucociliary clearance (MCC), a principle defense of airways against inhaled irritants and pathogens. The MCC apparatus consists of airway surface liquid (ASL), which has a mucus layer that traps pathogens to be removed by the coordinated beating of surface cilia [
1]. Physiologic levels of ASL and PCL determine the effectiveness of MCC, a process tightly regulated through CFTR activity [
2,
3]. As a result of reduced CFTR-mediated ion transport, CF airways fail to maintain optimal surface hydration and clear inhaled pathogens. Decreased MCC efficiency causes accumulation of thick mucus, opportunistic infections, and chronic inflammation. Beyond inherited defects, several different environmental insults can also negatively affect CFTR function even in those with normal genetics. For example, exposure to cigarette smoke is known to cause decreased CFTR activity in mice [
4], rats [
5], ferrets [
6], dogs [
7], and humans [
8,
9]. Reports also suggest excessive alcohol intake [
10] and exposure to cadmium [
11] and arsenic [
12,
13] result in diminished CFTR activity supporting the concept of ‘acquired CFTR dysfunction’. …