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Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocorticoids

Meghan Cundall1, Yongchang Sun, Christina Miranda

  • 1Department of Medicine, National Jewish Center and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206, USA.

The Journal of Allergy and Clinical Immunology
|December 6, 2003
PubMed
Abstract

Insights

Neutrophils in bronchoalveolar lavage fluid from severe asthma patients produce increased matrix metalloproteinase (MMP)-9, which is poorly inhibited by glucocorticoids (GCs). This study identifies neutrophils as a key source of MMP-9 in severe asthma.

Area of Science:

  • Pulmonary Medicine
  • Immunology
  • Biochemistry

Background:

  • Matrix metalloproteinase (MMP)-9 is elevated in bronchoalveolar lavage (BAL) fluid of severe asthma patients on high-dose glucocorticoids (GCs).
  • The precise source of this elevated MMP-9 and the impact of GCs remain unclear.

Purpose of the Study:

  • To identify neutrophils as the source of increased MMP-9 in BAL fluid from severe asthma patients.
  • To evaluate the effects of GCs on MMP-9 production and activity in severe asthma.

Main Methods:

  • Measurement of MMP-9 protein, activity, and mRNA in BAL fluid and cells from severe asthma patients and controls.
  • In vitro incubation with GCs.
  • Techniques included enzyme immunoassays, zymography, Western blotting, and real-time PCR.

Main Results:

  • High molecular weight (HMW) MMP-9 was significantly increased in severe asthma and correlated with BAL neutrophils.
  • BAL cell supernatant MMP-9 protein and HMW activity were elevated and correlated with neutrophils.
  • GCs showed a diminished inhibitory effect on MMP-9 in severe asthma compared to controls.

Conclusions:

  • Neutrophils in BAL fluid are a significant source of MMP-9 protein and activity in severe asthma.
  • Glucocorticoids exhibit limited efficacy in inhibiting neutrophil-derived MMP-9 in severe asthma.

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