The requirement for polymorphonuclear leukocytes in the late asthmatic response and heightened airways reactivity in an animal model.
The requirement for polymorphonuclear leukocytes in the late asthmatic response and heightened airways reactivity in an animal model.
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动物模型中晚期哮喘反应和气道反应性增强对多形核白细胞的需求。
DOI：
10.1164/arrd.1986.134.1.62
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Larsen,GL
中科院分区：
文献类型：
--
作者：
Murphy,KR;Wilson,MC;Irvin,CG;Glezen,LS;Marsh,WR;Haslett,C;Henson,PM;Larsen,GL
抗原诱导的晚期哮喘反应（LAR）以及该反应后气道反应性的增强与气道炎症的增加有关。采用我们实验室之前开发的兔子 LAR 动物模型，进行了 3 个阶段的实验，以研究多形核白细胞 (PML) 在 LAR 中的作用和增强的反应性。在所有 3 个阶段中，在用豚草提取物进行支气管激发前 3 天和后 3 天进行气道对组胺的反应性和支气管肺泡灌洗分析。在第一阶段，研究了两组接受氮芥的兔子：免疫组接受含有抗豚草IgE的免疫血清，对照组接受非免疫血清。在第二阶段，在主动脉闭塞期间向免疫兔子施用氮芥，使肺部暴露于氮芥，同时限制骨髓对该药物的暴露，从而防止 PML 耗竭。在第三阶段，与第一阶段一样，免疫组和非免疫组的兔子都接受了氮芥；然而，在抗原攻击之前，它们体内充满了富含中性粒细胞的 PML 群体。在所有实验中，没有一组对照（非免疫）兔子，无论是耗尽还是充满 PML，都出现立即哮喘反应 (IAR) 或 LAR。此外，豚草攻击后，灌洗细胞或气道反应性没有显着增加。相比之下，那些接受免疫血清和氮芥的动物出现了 IAR；然而，没有发生 LAR，也没有观察到气道反应性的显着变化。接受免疫血清和氮芥并主动脉闭塞的兔子出现 IAR 和 LAR，并且气道反应性增加。在抗原攻击前输注 PML 的 PML 耗尽的免疫兔也产生了 IAR 和 LAR，并且气道反应性在 3 天后显着增加。豚草攻击后 72 小时的灌洗分析显示，接受免疫血清和氮芥的主动脉闭塞动物的 PML 显着增加。然而，在没有主动脉闭塞的情况下接受免疫血清和氮芥的动物中，灌洗后的 PML 没有显着增加。豚草攻击后 72 小时，充满 PML 的动物灌洗 PML 也没有显着增加。这些观察结果表明，LAR 和随后气道反应性的增加取决于抗原攻击时 PML 的存在。
The antigen-induced late asthmatic response (LAR) and subsequent heightened airways reactivity after this response have been associated with increased airways inflammation. Employing an animal model of the LAR in rabbits previously developed in our laboratory, 3 phases of experiments were performed to investigate the role of polymorphonuclear leukocytes (PML) in the LAR and heightened reactivity. In all 3 phases, airways reactivity to histamine and bronchoalveolar lavage analysis were performed 3 days before and 3 days after bronchial challenge with ragweed extract. In Phase 1, 2 groups of rabbits receiving nitrogen mustard were studied: an immune group received immune serum containing antiragweed IgE, and a control group received nonimmune serum. In Phase II, nitrogen mustard was administered to immune rabbits during aortic occlusion to allow the lungs to be exposed to nitrogen mustard while limiting exposure of the bone marrow to this drug, preventing depletion of PML. In Phase III, both an immune and a nonimmune group of rabbits received nitrogen mustard as in Phase I; however, prior to antigen challenge, they were repleted with a neutrophil-rich population of PML. In all experiments, no group of control (nonimmune) rabbits, whether depleted or repleted of PML, developed an immediate asthmatic response (IAR) or a LAR. In addition, no significant increases in lavage cells or airways reactivity occurred after ragweed challenge. In contrast, those animals receiving immune serum and nitrogen mustard developed an IAR; however, no LAR occurred, and no significant change in airways reactivity was observed. Rabbits receiving immune serum and nitrogen mustard with aortic occlusion developed an IAR and LAR, and airways reactivity increased. The PML-depleted immune rabbits transfused with PML prior to antigen challenge also developed an IAR and a LAR, and airways reactivity increased markedly 3 days later. Lavage analysis 72 h after ragweed challenge showed animals that received immune serum and nitrogen mustard with aortic occlusion had a significant increase in PML. However, there was no significant increase in lavage PML in the animals receiving immune serum and nitrogen mustard without aortic occlusion. Animals repleted with PML also had no significant increase in lavage PML 72 h after ragweed challenge. These observations suggest that the LAR and subsequent increase in airways reactivity are dependent on the presence of PML at the time of antigen challenge.