title: Aggravation of Allergic Airway Inflammation by Cigarette Smoke in Mice Is CD44-Dependent.
abstract: BACKGROUND
  Although epidemiological studies reveal that cigarette smoke (CS) facilitates the development and exacerbation of allergic asthma, these studies offer limited information on the mechanisms involved. The transmembrane glycoprotein CD44 is involved in cell adhesion and acts as a receptor for hyaluronic acid and osteopontin. We aimed to investigate the role of CD44 in a murine model of CS-facilitated allergic airway inflammation.
  
  
  METHODS
  Wild type (WT) and CD44 knock-out (KO) mice were exposed simultaneously to house dust mite (HDM) extract and CS. Inflammatory cells, hyaluronic acid (HA) and osteopontin (OPN) levels were measured in bronchoalveolar lavage fluid (BALF). Proinflammatory mediators, goblet cell metaplasia and peribronchial eosinophilia were assessed in lung tissue. T-helper (Th) 1, Th2 and Th17 cytokine production was evaluated in mediastinal lymph node cultures.
  
  
  RESULTS
  In WT mice, combined HDM/CS exposure increased the number of inflammatory cells and the levels of HA and OPN in BALF and Th2 cytokine production in mediastinal lymph nodes compared to control groups exposed to phosphate buffered saline (PBS)/CS, HDM/Air or PBS/Air. Furthermore, HDM/CS exposure significantly increased goblet cell metaplasia, peribronchial eosinophilia and inflammatory mediators in the lung. CD44 KO mice exposed to HDM/CS had significantly fewer inflammatory cells in BALF, an attenuated Th2 cytokine production, as well as decreased goblet cells and peribronchial eosinophils compared to WT mice. In contrast, the levels of inflammatory mediators were similar or higher than in WT mice.
  
  
  CONCLUSIONS
  We demonstrate for the first time that the aggravation of pulmonary inflammation upon combined exposure to allergen and an environmental pollutant is CD44-dependent. Data from this murine model of concomitant exposure to CS and HDM might be of importance for smoking allergic asthmatics.
authors.affiliation: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Smitha
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Lanckacker
authors.affiliation: Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Mieke
authors.initials: M
authors.lastname: Dentener
authors.affiliation: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Ken
authors.initials: K
authors.lastname: Bracke
authors.affiliation: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sharen
authors.initials: S
authors.lastname: Provoost
authors.affiliation: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: De Grove
authors.affiliation: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Brusselle
authors.affiliation: Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Respiratory Medicine, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Emiel
authors.initials: E
authors.lastname: Wouters
authors.affiliation: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Tania
authors.initials: T
authors.lastname: Maes
authors.affiliation: Department of Respiratory Medicine, Laboratory for Translational Research in Obstructive Pulmonary Diseases, Ghent University Hospital, Ghent, Belgium.
authors.forename: Guy
authors.initials: G
authors.lastname: Joos
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000473:pathology; D020397:Goblet Cells / Q000473:pathology; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D006967:Hypersensitivity / Q000150:complications* / Q000276:immunology* / Q000469:parasitology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D008679:Metaplasia; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin / Q000378:metabolism; D011014:Pneumonia / Q000150:complications* / Q000276:immunology* / Q000469:parasitology; D039981:Pyroglyphidae / Q000276:immunology; D012907:Smoking / Q000009:adverse effects*; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D018960:Hyaluronan Receptors; D053495:Osteopontin; D006820:Hyaluronic Acid