Inflammatory lung secretions inhibit dendritic cell maturation and function via neutrophil elastase

Am J Respir Crit Care Med. 2006 Dec 1;174(11):1189-98. doi: 10.1164/rccm.200605-632OC. Epub 2006 Sep 7.


Rationale: Continuous episodes of infection are a feature of lung diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Lung antigen-presenting dendritic cells (DCs) sample inhaled antigen to initiate immune responses. Therefore, we hypothesized that inflammatory mediators, such as neutrophil elastase (NE) released into the lung, may be able to modulate their activity.

Objective: To determine whether sputum (from patients with COPD and those with CF) or NE can alter DC phenotype and function.

Method: NE and sputum samples were incubated with immature or mature murine DCs (mDCs). DC phenotype and function were studied by fluorescence-activated cell sorter and Western Blot analysis, assessing their expression of costimulatory molecules and their ability to induce T cell proliferation.

Results: COPD/CF sputum samples and human NE downregulated the expression of CD40, CD80, and CD86 (but not major histocompatibility complex II) on DCs and inhibited LPS-induced DC maturation. This effect was partially (sputa) to significantly (NE) reversed by addition of recombinant secretory leukocyte protease inhibitor. Western Blot analysis showed that purified NE degraded CD86 in mDC lysates in a time- and dose-dependent fashion, and caused shedding of CD86 into the supernatants of mDC cultures. NE treatment also inhibited the antigen-presenting ability of mDCs, as measured by their ability to induce ovalbumin-specific D011.10-transgenic T-cell proliferation.

Conclusions: Our data indicate that NE in lung inflammatory secretions of patients with COPD/CF may disable DCs and prevent them from mounting an adequate immune response. This may have implications for the infection-driven generation of disease exacerbations in these two pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antigen Presentation / immunology
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / physiology
  • Blotting, Western
  • CD40 Antigens / metabolism
  • Cystic Fibrosis / immunology
  • Cystic Fibrosis / physiopathology*
  • Cytokines / analysis
  • Dendritic Cells / immunology
  • Dendritic Cells / physiology*
  • Female
  • Humans
  • Immunohistochemistry
  • Leukocyte Elastase / immunology
  • Leukocyte Elastase / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Sputum / cytology


  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • Cytokines
  • Leukocyte Elastase