An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke

This international, peer-reviewed Open Access journal by Dove Medical Press focuses on pathophysiological processes underlying Chronic Obstructive Pulmonary Disease (COPD) interventions, patient focused education, and self-management protocols. Sign up for email alerts here.

39,063 Monthly downloads/views I 2.893 Impact Factor I 5.2 CiteScore I 1.16 Source Normalized Impact per Paper (SNIP) I 0.804 Scimago Journal & Country Rank (SJR)

Record: found
Abstract: found
Article: found

Is Open Access

An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke

research-article

Author(s): Shakti D Shukla ¹ , Rory L Fairbairn ¹ , David A Gell ¹ , Roger D Latham ¹ , Sukhwinder S Sohal ¹ ^, ² , Eugene H Walters ¹ , Ronan F O’Toole ¹

Publication date (Electronic): 25 July 2016

Journal: International Journal of Chronic Obstructive Pulmonary Disease

Publisher: Dove Medical Press

Keywords: airway epithelium, NTHi, pneumococci, WEB-2086, platelet-activating factor receptor, PAFr antagonist

Read this article at

ScienceOpenPublisher PMC

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

COPD is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. Tobacco smoking, the primary risk factor for the development of COPD, induces increased expression of platelet-activating factor receptor (PAFr) in the lung epithelium. Nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae adhere to PAFr on the luminal surface of human respiratory tract epithelial cells.

Objective

To investigate PAFr as a potential drug target for the prevention of infections caused by the main bacterial drivers of acute exacerbations in COPD patients, NTHi and S. pneumoniae.

Methods

Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE). PAFr expression levels were determined using immunocytochemistry and quantitative polymerase chain reaction. The epithelial cells were challenged with either NTHi or S. pneumoniae labeled with fluorescein isothiocyanate, and bacterial adhesion was measured using immunofluorescence. The effect of a well-evaluated antagonist of PAFr, WEB-2086, on binding of the bacterial pathogens to BEAS-2B cells was then assessed. In silico studies of the tertiary structure of PAFr and the binding pocket for PAF and its antagonist WEB-2086 were undertaken.

Results

PAFr expression by bronchial epithelial cells was upregulated by CSE, and significantly associated with increased bacterial adhesion. WEB-2086 reduced the epithelial adhesion by both NTHi and S. pneumoniae to levels observed for non-CSE-exposed cells. Furthermore, it was nontoxic toward the bronchial epithelial cells. In silico analyses identified a binding pocket for PAF/WEB-2086 in the predicted PAFr structure.

Conclusion

WEB-2086 represents an innovative class of candidate drugs for inhibiting PAFr-dependent lung infections caused by the main bacterial drivers of smoking-related COPD.

Most cited references 36

Record: found
Abstract: found
Article: not found

Developing COPD: a 25 year follow up study of the general population.

H Scharling, J Vestbo, A Løkke … (2006)

Smokers are more prone to develop chronic obstructive pulmonary disease (COPD) than non-smokers, but this finding comes from studies spanning 10 years or less. The aim of this study was to determine the 25 year absolute risk of developing COPD in men and women from the general population. As part of the Copenhagen City Heart Study, 8045 men and women aged 30-60 years with normal lung function at baseline were followed for 25 years. Lung function measurements were collected and mortality from COPD during the 25 year observation period was analysed. The percentage of men with normal lung function ranged from 96% of never smokers to 59% of continuous smokers; for women the proportions were 91% and 69%, respectively. The 25 year incidence of moderate and severe COPD was 20.7% and 3.6%, respectively, with no apparent difference between men and women. Smoking cessation, especially early in the follow up period, decreased the risk of developing COPD substantially compared with continuous smoking. During the follow up period there were 2912 deaths, 109 of which were from COPD. 92% of the COPD deaths occurred in subjects who were current smokers at the beginning of the follow up period. The absolute risk of developing COPD among continuous smokers is at least 25%, which is larger than was previously estimated.

0 comments Cited 163 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team.

J. Pekka Nuorti, Jay C. Butler, Monica M. Farley … (2000)

Approximately half of otherwise healthy adults with invasive pneumococcal disease are cigarette smokers. We conducted a population-based case-control study to assess the importance of cigarette smoking and other factors as risk factors for pneumococcal infections. We identified immunocompetent patients who were 18 to 64 years old and who had invasive pneumococcal disease (as defined by the isolation of Streptococcus pneumoniae from a normally sterile site) by active surveillance of laboratories in metropolitan Atlanta, Baltimore, and Toronto. Telephone interviews were conducted with 228 patients and 301 control subjects who were reached by random-digit dialing. Fifty-eight percent of the patients and 24 percent of the control subjects were current smokers. Invasive pneumococcal disease was associated with cigarette smoking (odds ratio, 4.1; 95 percent confidence interval, 2.4 to 7.3) and with passive smoking among nonsmokers (odds ratio, 2.5; 95 percent confidence interval, 1.2 to 5.1) after adjustment by logistic-regression analysis for age, study site, and independent risk factors such as male sex, black race, chronic illness, low level of education, and living with young children who were in day care. There were dose-response relations for the current number of cigarettes smoked per day, pack-years of smoking, and time since quitting. The adjusted population attributable risk was 51 percent for cigarette smoking, 17 percent for passive smoking, and 14 percent for chronic illness. Cigarette smoking is the strongest independent risk factor for invasive pneumococcal disease among immunocompetent, nonelderly adults. Because of the high prevalence of smoking and the large population attributable risk, programs to reduce both smoking and exposure to environmental tobacco smoke have the potential to reduce the incidence of pneumococcal disease.

0 comments Cited 153 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Not 15 but 50% of smokers develop COPD?--Report from the Obstructive Lung Disease in Northern Sweden Studies.

Kara M. Lindstrom, L Larsson, E Rönmark … (2003)

The prevalence of chronic obstructive pulmonary disease (COPD) according to guidelines of today seems considerably higher than has been reported also in recent literature. To estimate the prevalence of COPD as defined by British Thoracic Society (BTS) criteria and the recent global initiative for chronic obstructive lung disease (GOLD) criteria. Further aims were to assess the proportion of underdiagnosis and of symptoms in subjects with COPD, and to study risk factors for COPD. In 1996, 5892 of the Obstructive Lung Disease in Northern Sweden (OLIN) Study's first cohort could be traced to a third follow-up survey, and 5189 completed responses (88%) were received corresponding to 79% of the original cohort from December 1985. Of the responders, a random sample of 1500 subjects were invited to a structured interview and a lung function test, and 1237 of the invited completed a lung function test with acceptable quality. In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, while it was 14% according to the GOLD criteria. The absolutely dominating risk factors were increasing age and smoking, and approximately a half of elderly smokers fulfilled the criteria for COPD according to both the BTS and the GOLD criteria. Family history of obstructive airway disease was also a risk factor, while gender was not. Of those fulfilling the BTS criteria for COPD, 94% were symptomatics, 69% had chronic productive cough, but only 31% had prior to the study been diagnosed as having either chronic bronchitis, emphysema, or COPD. The corresponding figures for COPD according GOLD were 88, 51, and 18%. In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, and it was 14% according to the GOLD criteria. Fifty percent of elderly smokers had developed COPD. The large majority of subjects having COPD were symptomatic, while the proportion of those diagnosed as having COPD or similar diagnoses was small.

0 comments Cited 138 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Int J Chron Obstruct Pulmon Dis

Journal ID (iso-abbrev): Int J Chron Obstruct Pulmon Dis

Journal ID (publisher-id): International Journal of COPD

Title: International Journal of Chronic Obstructive Pulmonary Disease

Publisher: Dove Medical Press

ISSN (Print): 1176-9106

ISSN (Electronic): 1178-2005

Publication date Collection: 2016

Publication date (Electronic): 25 July 2016

Volume: 11

Pages: 1647-1655

Affiliations

[1 ]Breathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia

[2 ]School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia

Author notes

Correspondence: Ronan F O’Toole, Breathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Medical Science 1, 17 Liverpool Street, Hobart, TAS 7000, Australia, Tel +61 3 6226 6974, Email ronan.otoole@ 123456utas.edu.au

[*]

These authors contributed equally to this work

Article

Publisher ID: copd-11-1647

DOI: 10.2147/COPD.S108698

PMC ID: 4965220

PubMed ID: 27524890

SO-VID: b76de183-34d1-4732-8553-87c322284a84

License:

The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

International Journal of COPD (submit here)

An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke

Read this article at

Abstract

Background

Objective

Methods

Results

Conclusion

Most cited references 36

Developing COPD: a 25 year follow up study of the general population.

Cigarette smoking and invasive pneumococcal disease. Active Bacterial Core Surveillance Team.

Not 15 but 50% of smokers develop COPD?--Report from the Obstructive Lung Disease in Northern Sweden Studies.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 265

Cited by 19

Most referenced authors 557