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Cigarette smoke and platelet-activating factor receptor dependent adhesion of Streptococcus pneumoniae to lower airway cells
  1. Jonathan Grigg1,
  2. Haydn Walters2,
  3. Sukhwinder Singh Sohal2,
  4. Richard Wood-Baker2,
  5. David W Reid2,
  6. Cang-Bao Xu3,
  7. Lars Edvinsson3,
  8. Mathieu C Morissette4,
  9. Martin R Stämpfli4,
  10. Michael Kirwan1,
  11. Lee Koh1,
  12. Reetika Suri1,
  13. Naseem Mushtaq1
  1. 1Centre for Paediatrics, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  2. 2NHMRC National Centre for Research Excellence in Chronic Respiratory Disease, Menzies Research Institute, Hobart, Australia
  3. 3Division of Experimental Vascular Research, Institute of Clinical Science in Lund, Lund University, Lund, Sweden
  4. 4Departments of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Professor Jonathan Grigg, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary, University of London, 4 Newark Street, London E1 2AT, UK; j.grigg{at}


Background Exposure to cigarette smoke (CS) is associated with increased risk of pneumococcal infection. The mechanism for this association is unknown. We recently reported that the particulate matter from urban air simulates platelet-activating factor receptor (PAFR)-dependent adhesion of pneumococci to airway cells. We therefore sought to determine whether CS stimulates pneumococcal adhesion to airway cells.

Methods Human alveolar (A549), bronchial (BEAS2-B), and primary bronchial epithelial cells (HBEpC) were exposed to CS extract (CSE), and adhesion of Streptococcus pneumoniae determined. The role of PAFR in mediating adhesion was determined using a blocker (CV-3988). PAFR transcript level was assessed by quantitative real-time PCR, and PAFR expression by flow cytometry. Lung PAFR transcript level was assessed in mice exposed to CS, and bronchial epithelial PAFR expression assessed in active-smokers by immunostaining.

Results In A549 cells, CSE 1% increased pneumococcal adhesion (p<0.05 vs control), PAFR transcript level (p<0.01), and PAFR expression (p<0.01). Pneumococcal adhesion to A549 cells was attenuated by CV-3988 (p<0.001). CSE 1% stimulated pneumococcal adhesion to BEAS2-B cells and HBEpC (p<0.01 vs control). CSE 1% increased PAFR expression in BEAS2-B (p<0.01), and in HBEpC (p<0.05). Lung PAFR transcript level was increased in mice exposed to CS in vivo (p<0.05 vs room air). Active smokers (n=16) had an increased percentage of bronchial epithelium with PAFR-positive cells (p<0.05 vs never smokers, n=11).

Conclusion CSE stimulates PAFR-dependent pneumococcal adhesion to lower airway epithelial cells. We found evidence that CS increases bronchial PAFR in vivo.

  • Cigarette smoke
  • platelet-activating factor receptor
  • Streptococcus pneumoniae
  • adhesion
  • airway epithelial cells
  • asthma
  • macrophage biology
  • paediatric asthma
  • paediatric lung disease
  • paediatric physician
  • asthma epidemiology
  • asthma guidelines
  • asthma mechanisms
  • asthma pharmacology
  • bronchoscopy
  • COPD pathology
  • COPD pharmacology
  • airway epithelium
  • COPD exacerbations
  • emphysema
  • cystic fibrosis
  • innate immunity
  • respiratory infection
  • aspergillus lung disease
  • assisted ventilation
  • asthma genetics
  • bacterial infection
  • pneumonia
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  • Funding This work was supported by the Barts and the London Charity, and grants from the Swedish Research Council (number 05958), and the Royal Hobart Hospital Research Foundation, and NHMRC Australia.

  • Competing interests None.

  • Ethics approval Human Research Ethics Committee (Tasmania) Network (approval number: H0007017).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Raw data will be provided on request.

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