title: Platelet-activating factor receptor (PAFr) is upregulated in small airways and alveoli of smokers and COPD patients.
abstract: OBJECTIVE
  PAFr is a cell adhesion site for specific bacteria, notably non-typeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae. We previously published that PAFr expression is significantly upregulated in the large airways of smokers, especially in COPD. We have now investigated PAFr expression in the epithelium and Rbm of small airways and in the alveolar compartment in smokers and patients with both COPD and small airway disease.
  
  
  METHODS
  We evaluated PAFr expression cross-sectionally in resected lung tissue from: eight smokers with normal lung function (NLFS); 10 with smoking-related small airway narrowing only; eight COPD smokers; 10 COPD ex-smokers, and compared these with nine control tissues. Anti-PAFr immunostaining was quantified using computer-aided image analysis.
  
  
  RESULTS
  Significantly increased PAFr expression in small airway epithelium of all clinical groups was found compared with controls (P < 0.01). Moreover, epithelial PAFr expression was upregulated in COPD smokers compared with NLFS (P < 0.05), but not when compared with COPD ex-smokers or patients with only small airways disease. Smoking history (pack-year) correlated significantly with PAFr expression in the currently smoking individuals, especially in NLFS (r = 0.9; P < 0.002). An increase above normal in PAFr-expressing cells in the airway epithelial Rbm was only significant in COPD smokers (P < 0.007). An upregulation of PAFr-expressing cell in alveolar epithelium was uniformly found in all clinical groups compared with normal control (P < 0.01).
  
  
  CONCLUSIONS
  Epithelial PAFr expression is upregulated in small airways and alveoli in smokers and COPD. Increased expression of PAFr could be crucial in facilitating acute and chronic respiratory infection with specific respiratory pathogens.
authors.affiliation: NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Shakti Dhar
authors.initials: SD
authors.lastname: Shukla
authors.affiliation: NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Hans Konrad
authors.initials: HK
authors.lastname: Muller
authors.affiliation: NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Latham
authors.affiliation: NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.|School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia.
authors.forename: Sukhwinder Singh
authors.initials: SS
authors.lastname: Sohal
authors.affiliation: NHMRC Centre of Research Excellence for Chronic Respiratory Disease, School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: Eugene Haydn
authors.initials: EH
authors.lastname: Walters
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012313:RNA / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis / Q000235:genetics*; D020545:Respiratory Mucosa / Q000378:metabolism; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D012313:RNA
keywords: airway epithelium; chronic obstructive pulmonary disease; inhaled corticosteroid; platelet-activating factor receptor; ‘respiratory’ bacteria adhesion