Scuri Mario, Abraham William M
Division of Pulmonary and Critical Care Medicine, University of Miami at Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, FL 33140, USA.
Pulm Pharmacol Ther. 2003;16(6):335-40. doi: 10.1016/S1094-5539(03)00089-0.
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 150 kD-HA (LKDHA; 3 and 15 mg), or a 300 kD-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 150-300 kD, dose rather than molecular weight may be the most important determinant of pretreatment time resulting in a protective effect.
透明质酸（HA）可阻断对猪蛔虫抗原气道过敏的绵羊吸入猪胰弹性蛋白酶诱导的支气管收缩。由于与人类酶相比，其他物种的弹性蛋白酶可能表现出不同的催化特性，因此我们测试了HA对人中性粒细胞弹性蛋白酶（HNE）诱导的气道反应的疗效。我们测量了过敏性绵羊在单独吸入HNE之前和之后以及用150 kD - HA（LKDHA；3和15 mg）或300 kD - HA（HKDHA；6、7.5和15 mg）预处理后的肺阻力。HKDHA（3 mg）在HNE激发前0.5、4或8小时给予；LKDHA（15 mg）和HKDHA（6、7.5和15 mg）在激发前8小时给予。HNE引起急性支气管收缩，在激发前0.5或4小时给予3 mg LKDHA可阻断该收缩。激发前8小时给予LKDHA（3 mg）无效，但将剂量增加到15 mg可实现保护作用。当在激发前8小时给予6、7.5和15 mg的HKDHA时，观察到对HNE诱导的气道反应的剂量依赖性抑制。我们得出结论，HA可抑制HNE诱导的气道反应，并且在150 - 300 kD范围内，剂量而非分子量可能是导致保护作用的预处理时间的最重要决定因素。
