Hyaluronan blocks human neutrophil elastase (HNE)-induced airway responses in sheep

Mario Scuri, William M. Abraham

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Hyaluronan (HA) blocks inhaled porcine pancreatic elastase-induced bronchoconstriction in sheep with airway hypersensitivity to Ascaris suum antigen. Since elastases from other species may display different catalytic properties compared to the human enzyme, we tested the efficacy of HA on human neutrophil elastase (HNE)-induced airway responses. We measured pulmonary resistance in allergic sheep before and after inhalation of HNE alone and after pretreatment with a 150kD-HA (LKDHA; 3 and 15 mg), or a 300kD-HA (HKDHA; 6, 7.5, and 15 mg). HKDHA (3 mg) was given either 0.5, 4, or 8 h before HNE challenge; LKDHA (15 mg) and HKDHA (6, 7.5, and 15 mg) were given 8 h before challenge. HNE caused an acute bronchoconstriction which was blocked by 3 mg LKDHA given 0.5 or 4 h before challenge. LKDHA (3 mg) given 8 h before challenge was ineffective, but protection was achieved by increasing the dose to 15 mg. When HKDHA at 6, 7.5, and 15 mg was given 8 h before challenge a dose-dependent inhibition of the HNE-induced airway response was observed. We conclude that HA inhibits HNE-induced airway responses and that within the range of 150-300kD, dose rather than molecular weight may be the most important determinant of pretreatment time resulting in a protective effect.

Original languageEnglish (US)
Pages (from-to)335-340
Number of pages6
JournalPulmonary Pharmacology and Therapeutics
Volume16
Issue number6
DOIs
StatePublished - Dec 2003

Keywords

  • Asthma
  • Bradykinin
  • Elastase
  • Hyaluronan
  • Proteases

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology

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