TY - JOUR
T1 - Hyaluronan blocks human neutrophil elastase (HNE)-induced airway responses in sheep
AU - Scuri, Mario
AU - Abraham, William M.
PY - 2003/12
Y1 - 2003/12
N2 - 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.
AB - 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.
KW - Asthma
KW - Bradykinin
KW - Elastase
KW - Hyaluronan
KW - Proteases
UR - http://www.scopus.com/inward/record.url?scp=0142199892&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0142199892&partnerID=8YFLogxK
U2 - 10.1016/S1094-5539(03)00089-0
DO - 10.1016/S1094-5539(03)00089-0
M3 - Article
C2 - 14580924
AN - SCOPUS:0142199892
VL - 16
SP - 335
EP - 340
JO - Pulmonary Pharmacology and Therapeutics
JF - Pulmonary Pharmacology and Therapeutics
SN - 1094-5539
IS - 6
ER -