Second-Hand Cigarette Smoke Impairs Bacterial Phagocytosis in Macrophages by Modulating CFTR Dependent Lipid-Rafts

Ni, Inzer; Ji, Changhoon; Vij, Neeraj

doi:10.1371/journal.pone.0121200

Cited by 47 publications

(52 citation statements)

References 72 publications

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“…The disease kills more than 120,000 Americans each year and the number of people with COPD is increasing [56]. Each year, about 300,000 people die in Europe due to COPD [77], and the morbidity, disability, economic and social impact of COPD is substantial and increasing. The…”

Section: Copdmentioning

confidence: 99%

“…The loss of CFTR function induced by cigarette smoke exposure is also associated with loss of lipid raft CFTR, increased membrane ceramide accumulation and increased apoptosis [76]. It has also been shown that altered CFTR lipid rafts in macrophage exposed to cigarette smoke impair macrophage bacterial phagocytosis and killing, which might contribute to recurrent bacterial infections in the disease [77]. Interestingly, it has been reported that COPD patients with a history of disease exacerbations during the past year exhibited less CFTR function than those without a history of exacerbations, further emphasizing the clinical consequences associated with acquired CFTR dysfunction in COPD [67].…”

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confidence: 99%

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CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease

Fernández

Santi

Rose

et al. 2018

Expert Review of Respiratory Medicine

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Obstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) are causes of high morbidity and mortality worldwide. CF is a multiorgan genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is characterized by progressive chronic obstructive lung disease. Most cases of COPD are a result of noxious particles, mainly cigarette smoke but also other environmental pollutants. Areas covered: Although the pathogenesis and pathophysiology of CF and COPD differ, they do share key phenotypic features and because of these similarities there is great interest in exploring common mechanisms and/or factors affected by CFTR mutations and environmental insults involved in COPD. Various molecular, cellular and clinical studies have confirmed that CFTR protein dysfunction is common in both the CF and COPD airways. This review provides an update of our understanding of the role of dysfunctional CFTR in both respiratory diseases. Expert commentary: Drugs developed for people with CF to improve mutant CFTR function and enhance CFTR ion channel activity might also be beneficial in patients with COPD. A move toward personalized therapy using, for example, microRNA modulators in conjunction with CFTR potentiators or correctors, could enhance treatment of both diseases.

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Section: Copdmentioning

confidence: 99%

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confidence: 99%

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease

Fernández

Santi

Rose

et al. 2018

Expert Review of Respiratory Medicine

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“…al., have shown that SHS significantly reduces phagocytic clearance of pathogenic bacteria by affecting CFTR function in macrophages, extending potential manifestations beyond the airway. 89 The detrimental effects of SHS warrant further investigation into the mechanistic basis and physiologic significance underlying airway epithelial dysfunction in passive smokers, including its potential to contribute to COPD and respiratory infections, such as acute bronchitis or otitis media in the young. 90,91 …”

Section: Second Hand Smokingmentioning

confidence: 99%

Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis and Other Diseases of Mucus Clearance

Raju

Solomon

Dransfield

et al. 2016

Clinics in Chest Medicine

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Summary Chronic obstructive pulmonary disease (COPD) is a major public health problem accounting for more than 100,000 deaths and 750,000 hospitalizations each year in the United States alone. Though bronchodilators, inhaled steroids and other anti-inflammatory drugs can improve symptoms and reduce the risk of exacerbations, no therapies alter the natural history of the disease. This is the result of a number of factors including our poor understanding of the pathobiologic processes that drive specific COPD phenotypes, which has hindered drug development. Chronic bronchitis is perhaps the most clinically troublesome phenotype as most patients with COPD complain of cough and sputum production, and yet there are no effective treatments to target the mucus hypersecretion, accumulation and poor clearance that lead to these symptoms. Though it is well known that the absence of cystic fibrosis (CF) transmembrane receptor (CFTR) is the cause of CF, the prototypical disease of impaired mucociliary clearance, emerging data strongly suggest cigarette smoke and its components can lead to acquired CFTR dysfunction. Findings in vitro, in animal models, as well smokers with and without COPD also exhibit acquired CFTR dysfunction, which is associated with chronic bronchitis. This abnormality is not only present in the airways but is also present in extrapulmonary organs, suggesting CFTR dysfunction may contribute to smoking related lung disease as well as commonly associated comorbidities in which CFTR has a role. The development of potent CFTR modulators for the treatment of CF has made these findings clinically relevant as they may also have a role in treating COPD and other diseases of mucus clearance.

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“…This implies CFTR dysfunction by SHS may also account for increased infectious burden among passive smokers [47]. Consistent with this notion, Ni et al have reported that SHS significantly reduces phagocytic clearance of bacteria by depleting membrane expression of CFTR in macrophages extending the pathologic significance of CFTR dysfunction beyond the airway epithelium [48].…”

Section: Discussionmentioning

confidence: 81%

Evaluation of secondhand smoke effects on CFTR function in vivo

et al. 2020

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Background 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'. Secondhand smoke (SHS) exposure is an important health concern for many never smokers [14]. In spite of regulations limiting smoking in many public places, there are 1.8 billion non-smokers around the world that are frequently exposed to SHS resulting in more than 600,000 deaths per year [15, 16]. Exposure to SHS is a risk factor for respiratory infections and pulmonary diseases including lung cancer, asthma, and chronic obstructive pulmonary disease (COPD), the third leading cause of death in the U. S [17-20]. However, there is currently a limited understanding of how SHS exposure alters lung physiology to cause these diseases. Savitski et al. reported that SHS exposure, like mainstream smoking, results in decreased CFTR anion transport in human bronchial epithelial cells [21], suggesting CFTR abnormality may explain delayed mucociliary clearance and increased disease burden in never smokers [22, 23]. However, the observation of SHS-induced defects in CFTR is yet to be verified in a suitable animal model. Moreover, the functional consequences of such CFTR dysfunction on mucus physiology remain unexplored. To address these important follow-up questions, we have monitored CFTR-mediated ion transport in A/J mice exposed to SHS. We have previously found that A/ J mice exhibit susceptibility to smoking induced changes in CFTR function in a dose-dependent manner [4]. Based on these data, we have used A/J mice as an in vivo model to test the hypothesis that SHS reduces CFTR function and disrupts physiologically optimal airwa...

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Second-Hand Cigarette Smoke Impairs Bacterial Phagocytosis in Macrophages by Modulating CFTR Dependent Lipid-Rafts

Cited by 47 publications

References 72 publications

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease

CFTR dysfunction in cystic fibrosis and chronic obstructive pulmonary disease

Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis and Other Diseases of Mucus Clearance

Evaluation of secondhand smoke effects on CFTR function in vivo

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