Jarreau P H, Harf A, Levame M, Lambré C R, Lorino H, Macquin-Mavier I
Département de Physiologie, Service de Pharmacologie Clinique, Créteil, France.
Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):906-10. doi: 10.1164/ajrccm/145.4_Pt_1.906.
We investigated the effects of neuraminidase, a viral enzyme that cleaves alpha ketosidic cell-bound sialic acids, to see if it accounts for parainfluenza and influenza virus-induced airway hyperreactivity. Accordingly, Vibrio cholerae neuraminidase was administered intratracheally in guinea pigs, and airway reactivity was assessed 3 h later. Removal of sialic acid residues was evaluated by histologic studies. Airway responsiveness was determined in anesthetized, tracheotomized, and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized bronchoconstrictor agents. Respiratory system conductance was measured by the occlusion method. Neuraminidase injected intratracheally did not change airway reactivity to 10(-4) to 10(-2) M acetylcholine or 10(-4) to 2.5 x 10(-3) M histamine; nor did it prevent aerosolized albuterol from inhibiting histamine-induced bronchoconstriction. Substance P (10(-6) to 5 x 10(-5) M) had no significant bronchoconstrictor effect on guinea pigs pretreated with saline or neuraminidase. In guinea pigs pretreated with aerosols of the neutral endopeptidase inhibitor phosphoramidon (10(-4) M) before the concentration curve to aerosolized substance P was recorded, neuraminidase significantly reduced substance P-induced bronchoconstriction. When bronchoconstriction was induced by the 4-11 fragment of substance P (10(-5) to 10(-2) M), which is devoid of positive charges, it did not differ significantly in guinea pigs pretreated with saline and those pretreated with neuraminidase. These results indicate that in the guinea pig, neuraminidase injected intratracheally does not induce non-specific airway hyperreactivity and may alter the binding of substance P to its receptors.
我们研究了神经氨酸酶（一种可裂解与细胞结合的α酮糖苷唾液酸的病毒酶）的作用，以确定其是否与副流感病毒和流感病毒诱导的气道高反应性有关。因此，将霍乱弧菌神经氨酸酶经气管内注入豚鼠体内，并于3小时后评估气道反应性。通过组织学研究评估唾液酸残基的去除情况。通过将麻醉、气管切开并机械通气的豚鼠暴露于浓度递增的雾化支气管收缩剂中来测定气道反应性。采用阻断法测量呼吸系统传导率。经气管内注射的神经氨酸酶并未改变气道对10^(-4)至10^(-2)M乙酰胆碱或10^(-4)至2.5×10^(-3)M组胺的反应性；也未阻止雾化沙丁胺醇抑制组胺诱导的支气管收缩。P物质（10^(-6)至5×10^(-5)M）对用生理盐水或神经氨酸酶预处理的豚鼠无明显支气管收缩作用。在记录雾化P物质浓度曲线之前，先用中性内肽酶抑制剂磷酰胺素（10^(-4)M）气雾剂预处理豚鼠，神经氨酸酶可显著降低P物质诱导的支气管收缩。当由不带正电荷的P物质4-11片段（10^(-5)至10^(-2)M）诱导支气管收缩时，用生理盐水预处理的豚鼠和用神经氨酸酶预处理的豚鼠之间无显著差异。这些结果表明，在豚鼠中，经气管内注射神经氨酸酶不会诱导非特异性气道高反应性，且可能改变P物质与其受体的结合。
