Haemophilus influenzae lysate induces aspects of the chronic obstructive pulmonary disease phenotype

Seyed Javad Moghaddam, Cecilia G. Clement, M. Miguelina De La Garza, Xiaoyan Zou, Elizabeth L. Travis, Hays W.J. Young, Christopher M. Evans, Michael J. Tuvim, Burton F. Dickey

Research output: Contribution to journalArticle

72 Scopus citations

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-α was examined by transgenic airway overexpression and use of an inhibitory antibody. NTHi lysate induced rapid activation of NF-κB 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-α caused BALF neutrophilia and inflammatory cell infiltration around airways, but not fibrosis, and TNF-α 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-α 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.

Original languageEnglish (US)
Pages (from-to)629-638
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume38
Issue number6
DOIs
StatePublished - Jun 1 2008

Keywords

  • Bronchiolitis
  • Chronic obstructive
  • Fibrosis
  • Haemophilus influenzae
  • Inflammation
  • Pulmonary disease

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Moghaddam, S. J., Clement, C. G., De La Garza, M. M., Zou, X., Travis, E. L., Young, H. W. J., Evans, C. M., Tuvim, M. J., & Dickey, B. F. (2008). Haemophilus influenzae lysate induces aspects of the chronic obstructive pulmonary disease phenotype. American journal of respiratory cell and molecular biology, 38(6), 629-638. https://doi.org/10.1165/rcmb.2007-0366OC