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Elastase contributes to antigen-induced mucociliary dysfunction in ovine airways
T G O'Riordan1, R Otero, Y Mao
1Pulmonary Division, University of Miami at Mount Sinai Medical Center, Miami Beach, Florida 33140, USA.
Summary
Neutrophil elastase contributes to antigen-induced airway dysfunction by impairing mucociliary clearance. Elastase inhibitors, such as alpha1-protease inhibitor, can protect against this impairment, suggesting therapeutic potential.
Area of Science:
- Respiratory Physiology
- Immunology
- Pharmacology
Background:
- Antigen exposure triggers bronchoconstriction and impairs mucociliary clearance.
- Neutrophil influx into airways correlates with early mucociliary dysfunction.
- Neutrophil-derived elastase is a potential mediator of this dysfunction.
Purpose of the Study:
- To test if neutrophil elastase contributes to acute antigen-induced mucociliary dysfunction.
- To evaluate the efficacy of elastase inhibitors in preventing this dysfunction.
Main Methods:
- Measurement of tracheal mucous velocity (TMV) in sheep using roentgenography.
- Airway challenge with Ascaris suum antigen.
- Pretreatment with alpha1-protease inhibitor (alpha1-PI) or neutrophil elastase inhibitor (ICI 200,355).
- Bronchoalveolar lavage (BAL) to assess neutrophil count and elastase activity.
Main Results:
- Antigen challenge significantly reduced TMV.
- alpha1-PI and ICI 200,355 attenuated antigen-induced TMV reduction.
- Inactivated alpha1-PI did not provide protection.
- Inhaled elastase decreased TMV, an effect blocked by alpha1-PI.
- BAL confirmed increased neutrophils and elastase activity post-antigen challenge.
Conclusions:
- Antigen-induced impairment of mucociliary clearance is partly mediated by neutrophil elastase.
- Elastase inhibitors show promise in protecting against acute antigen-induced mucociliary dysfunction.