title: Haemophilus influenzae lysate induces aspects of the chronic obstructive pulmonary disease phenotype.
abstract: Nontypeable Haemophilus influenzae (NTHi) commonly colonizes the lower airways of patients with chronic obstructive pulmonary disease (COPD). Whether it contributes to COPD progression is unknown. Here, we determined which aspects of the COPD phenotype can be induced by repetitive exposure to NTHi products. Mice were exposed weekly to an aerosolized NTHi lysate, and inflammation was evaluated by measurement of cells and cytokines in bronchoalveolar lavage fluid (BALF) and immunohistochemical staining; structural changes were evaluated histochemically by periodic acid fluorescent Schiff's reagent, Masson's trichrome, and Picrosirius red staining; mucin gene expression was measured by quantitative RT-PCR; and the role of TNF-alpha was examined by transgenic airway overexpression and use of an inhibitory antibody. NTHi lysate induced rapid activation of NF-kappaB in airway cells and increases of inflammatory cytokines and neutrophils in BALF. Repetitive exposure induced infiltration of macrophages, CD8+ T cells, and B cells around airways and blood vessels, and collagen deposition in airway and alveolar walls, but airway mucin staining and gel-forming mucin transcripts were not increased. Transgenic overexpression of TNF-alpha caused BALF neutrophilia and inflammatory cell infiltration around airways, but not fibrosis, and TNF-alpha neutralization did not reduce BALF neutrophilia in response to NTHi lysate. In conclusion, NTHi products elicit airway inflammation in mice with a cellular and cytokine profile similar to that in COPD, and cause airway wall fibrosis but not mucous metaplasia. TNF-alpha is neither required for inflammatory cell recruitment nor sufficient for airway fibrosis. Colonization by NTHi may contribute to the pathogenesis of small airways disease in patients with COPD.
authors: Department of Pulmonary Medicine, University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.
authors: Seyed Javad
authors: SJ
authors: Moghaddam
authors: Cecilia G
authors: CG
authors: Clement
authors: M Miguelina
authors: MM
authors: De la Garza
authors: Xiaoyan
authors: X
authors: Zou
authors: Elizabeth L
authors: EL
authors: Travis
authors: Hays W J
authors: HW
authors: Young
authors: Christopher M
authors: CM
authors: Evans
authors: Michael J
authors: MJ
authors: Tuvim
authors: Burton F
authors: BF
authors: Dickey
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D006193:Haemophilus influenzae / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000821:virology; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000473:pathology; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014598:Uteroglobin / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D009077:Mucins; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D014598:Uteroglobin