DIFFERENTIAL SUSCEPTIBILITY TO OZONE-INDUCED AIRWAYS HYPERREACTIVITY IN INBRED STRAINS OF MICE
DIFFERENTIAL SUSCEPTIBILITY TO OZONE-INDUCED AIRWAYS HYPERREACTIVITY IN INBRED STRAINS OF MICE
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DOI：
10.3109/01902149509031755
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发表时间：
1995-07-01
影响因子：
1.7
通讯作者：
KLEEBERGER, SR
中科院分区：
文献类型：
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作者：
ZHANG, LY;LEVITT, RC;KLEEBERGER, SR
具有高度气道反应性的个体，例如哮喘患者，可能处于氧化剂空气污染物的炎症效应的风险中。在近交系小鼠中，以前已经描述了呼吸道对乙酰胆碱（ACh）的反应性和对臭氧（O-3）诱导的呼吸道炎症的不同易感性的显著品系间差异。本研究使用这些小鼠模型来检验以下假设：（1）O-3诱导的对ACh的高反应性是固有的基线ACh反应性的函数，以及（2）对O-3诱导的炎症的易感性与O-3诱导的高反应性相关。将具有高反应性（DBA/2 J、AKR/J、A/J）、低反应性（C3 H/HeJ、C57 BL/6 J、SJL/J）或中间（129/J）ACh反应性表型的菌株（15-25 g，6-8周）暴露于2.0 ppm O-3或空气（对照）3 h。乙酰胆碱反应性（25和50 μ g/kg，IV）进行了评估0和24小时后曝光。与空气对照组相比，在高反应性A/J菌株中，O-3后24小时对25和50 μ g/kg ACh的平均气道反应显著增加（p <0.05）。在低反应性菌株中，O-3显著（p <0.05）增加了C57 BL/6 J和SJL/J菌株对50 μ g/kg ACh的反应。A/J、C57 BL/6 J和SJL/J小鼠对O-3诱导的肺损伤易感。O-3没有改变其他菌株的ACh反应性。O-3也没有影响气道反应乙酰甲胆碱或卡巴胆碱，观察结果与假设一致，O-3诱导的高反应性乙酰胆碱可能是由于，部分，O-3对胆碱酯酶功能的影响。用免疫抑制剂（环磷酰胺）或抗PMN抗体治疗C57 BL/6 J和A/J小鼠，可显著（p <0.05）减弱循环和浸润性多形核白细胞（PMN），但不影响O-3诱导的高反应性。因此，O-3诱导的ACh高反应性不是基线反应性的函数，而是与急性O-3诱导的气道损伤和炎症的易感性相关。药理学研究表明，虽然中性粒细胞与O-3诱导的高反应性，这些细胞的原因的影响，这两个事件是不相互依赖的。
Individuals with heightened airways reactivity, such as asthmatics, may be at risk to inflammatory effects of oxidant air pollutants. In the inbred mouse, significant interstrain variation in airways reactivity to acetylcholine (ACh) and differential susceptibility to ozone (O-3)-induced airways inflammation has been described previously. This study used these murine models to test hypotheses that (1) O-3-induced hyperreactivity to ACh is a function of inherent baseline ACh reactivity, and (2) susceptibility to O-3-induced inflammation is associated with O-3-induced hyperreactivity. Strains (15-25 g, 6-8 weeks) with HYPERREACTIVE (DBA/2J, AKR/J, A/J), HYPOREACTIVE (C3H/HeJ, C57BL/6J, SJL/J), or INTERMEDIATE (129/J) phenotypes for ACh reactivity were exposed for 3 h to 2.0 ppm O-3 or air (control). ACh reactivity (25 and 50 mu g/kg, IV) was assessed 0 and 24 h after exposure. Relative to air controls, mean airways responses to 25 and 50 mu g/kg ACh 24 h post-O-3 increased significantly in the HYPERREACTIVE A/J strain (p < .05). Among HYPOREACTIVE strains, O-3 significantly (p < .05) increased the response to 50 mu g/kg ACh in C57BL/6J and SJL/J strains 24 h postexposure. A/J, C57BL/6J, and SJL/J mice are susceptible to O-3-induced lung injury. O-3 did not alter ACh reactivity in the other strains. O-3 also did not affect airways reactivity to methacholine or carbachol, observations consistent with the hypothesis that O-3-induced hyperreactivity to ACh may be due, in part, to O-3 effects on cholinesterase function. Treatment of C57BL/6J and A/J mice with an immunosuppressant (cyclophosphamide) or an anti-PMN antibody significantly (p < .05) attenuated circulating and infiltrating polymorphonuclear leukocytes (PMNs), but did not affect O-3-induced hyperreactivity. Therefore, O-3-induced ACh hyperreactivity was not a function of baseline reactivity, but correlated with susceptibility to acute O-3-induced airways injury and inflammation. Pharmacologic studies suggest that although PMNs were associated with O-3-induced hyperreactivity, these cells were not the cause of the effect, and that these two events are not codependent.