title: Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa.
abstract: Airway inflammation represents a hallmark of the cystic fibrosis (CF) disease. However, the mucosal distribution of immune cells along the CF airways has not been clearly defined, particularly in intermediate bronchi and distal bronchioles. We analysed lung tissues collected at the time of transplantation from homozygous DeltaF508+/+CF patients versus non-CF donors. Using immunohistochemistry, the distribution of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, polymorphonuclear neutrophils (PMN), mast cells, CD3+ T cells, including the CD4+ and CD8+ subsets, CD20+ B cells, CD38+ plasma cells and CD68+ macrophages, was analysed at lobar, segmental and distal levels of the bronchial tree. Using image cytometry, the number of cells per mm2 was assessed in the depth of the bronchial wall. In CF airways, alterations mainly consisted in lesions of the surface epithelium. Numerous immune cells were heterogeneously distributed all along the bronchial tree and mainly located in the mucosa, beneath the surface epithelium. Compared to non-CF donors, the lymphoid aggregates formed by B cells were significantly larger all along the CF airways (P = 0.001). The number of T lymphocytes was higher at the CF distal level (P = 0.035), where we observed an intense tissue damage. PMN preferentially accumulated (P = 0.033) in the CF surface epithelium, which overexpressed ICAM-1 but not VCAM-1 and E-selectin. These results highlight the nature of the inflammatory infiltrate in the CF airway mucosa and emphasize a prominent implication of PMN, B and T lymphocytes in the CF disease.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherche (IFR) 53, Université de Reims Champagne-Ardenne, Reims, France.
authors.forename: C
authors.initials: C
authors.lastname: Hubeau
authors.forename: M
authors.initials: M
authors.lastname: Lorenzato
authors.forename: J P
authors.initials: JP
authors.lastname: Couetil
authors.forename: D
authors.initials: D
authors.lastname: Hubert
authors.forename: D
authors.initials: D
authors.lastname: Dusser
authors.forename: E
authors.initials: E
authors.lastname: Puchelle
authors.forename: D
authors.initials: D
authors.lastname: Gaillard
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015415:Biomarkers; D001980:Bronchi / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D001987:Bronchiectasis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D019040:E-Selectin / Q000032:analysis; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D016040:Lung Transplantation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D009092:Mucous Membrane / Q000276:immunology* / Q000473:pathology; D020556:Neutrophil Infiltration; D010950:Plasma Cells / Q000276:immunology / Q000473:pathology; D012141:Respiratory Tract Infections / Q000209:etiology / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1