PERSISTENT AIRWAY HYPERRESPONSIVENESS AND HISTOLOGIC ALTERATIONS AFTER CHRONIC ANTIGEN CHALLENGE IN CATS
PERSISTENT AIRWAY HYPERRESPONSIVENESS AND HISTOLOGIC ALTERATIONS AFTER CHRONIC ANTIGEN CHALLENGE IN CATS
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DOI：
10.1164/ajrccm.151.1.7812551
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发表时间：
1995-01-01
影响因子：
24.7
通讯作者：
LEFF, AR
中科院分区：
文献类型：
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作者：
PADRID, P;SNOOK, S;LEFF, AR
我们研究了慢性免疫致敏对最初的非特应性猫（一种自发发展为特发性哮喘的物种）的气道反应性和相关细胞学和组织学改变的影响。7只猫肌肉注射猪蛔虫抗原（AA）致敏4 wk，另4只猫作为假对照。通过致敏动物对雾化AA的反应增加证明了气道致敏（R（L）= 45.9 +/- 6.1 cm H2O/L/s，而基线反应为24.7 +/- 1.5 cm H2O/L/s，p < 0.01），AA后24 h对乙酰胆碱（ACh）激发的反应增加，表明高反应性（类似于PD 200中的1.0 log降低，p < 0.01）。致敏动物的支气管肺泡灌洗液（BAL）中的嗜酸性粒细胞数量增加了12倍（p < 0.01，与对照组相比）; 32 +/- 5%的BAL嗜酸性粒细胞的比密度< 1.050，而AA激发前为8 +/- 2%（p < 0.05）。对照组在用生理盐水假激发后24小时，气道反应性、嗜酸性粒细胞恢复或密度没有变化。同样的7只致敏猫进一步接受每周3次雾化AA，持续4至6周，然后再次采集BAL样本，并在最后一次雾化AA给药后72小时生成ACh剂量-反应曲线。气道高反应性增加（与PD 200中1.5 log下降相似，p < 0.001），BAL液中回收的嗜酸性粒细胞数量增加11倍（p < 0.05）。尸检标本显示AA激发动物的支气管收缩，但对照组没有;管腔狭窄伴有：（1）平滑肌厚度增加29.0 +/- 0.34%（p < 0.05）;（2）杯状细胞和粘膜下腺体肥大和增生;（3）上皮糜烂和嗜酸性粒细胞浸润。我们证明在非人类物种持续气道高反应性与一个完整的星座的组织学变化，上皮，平滑肌，粘液腺，和细胞学变化，在BAL液，所有诱导免疫致敏。我们的数据表明，慢性免疫致敏本身可能是导致慢性支气管哮喘相关变化的一个突出因素。
We studied the effect of chronic immune sensitization on the airway reactivity and associated cytologic and histologic alterations in initially nonatopic cats, a species that spontaneously develops idiopathic asthma. Seven cats were sensitized by intramuscular injection of Ascaris suum antigen (AA) for 4 wk, and four other cats served as sham controls. Airway sensitization was demonstrated by an increased response to nebulized AA in sensitized animals (R(L) = 45.9 +/- 6.1 cm H2O/L/s, versus a baseline response of 24.7 +/- 1.5 cm H2O/L/s, p < 0.01), and hyperresponsiveness was demonstrated by an increased response to acetylcholine (ACh)-challenge 24 h after AA (similar to 1.0 log decrease in PD200, p < 0.01). The number of eosinophils in the sensitized animals' bronchoalveolar lavage (BAL) fluid increased 12-fold (p < 0.01 versus control) in response to AA challenge; 32 +/- 5% of the BAL eosinophils had a specific density < 1.050, versus 8 +/- 2% prior to AA challenge (p < 0.05). There was no change in airway reactivity, eosinophil recovery, or density in the control group 24 h after sham challenge with saline. The same seven sensitized cats further received nebulized AA three times weekly for 4 to 6 wk, after which BAL samples were again obtained and ACh dose-response curves generated 72 h after the final administration of nebulized AA. Airway hyperresponsiveness increased (similar to 1.5 log decrease in PD200, p < 0.001) and the number of eosinophils recovered in BAL fluid was increased 11-fold (p < 0.05). Necropsy specimens demonstrated bronchoconstriction in AA-challenged animals but not controls; luminal narrowing was accompanied by: (1) a 29.0 +/- 0.34% increase in smooth-muscle thickness (p < 0.05); (2) goblet-cell and submucosal-gland hypertrophy and hyperplasia; and (3) epithelial erosion and eosinophilic infiltration. We demonstrate in nonhuman species persistent airway hyperreactivity associated with a complete constellation of histologic changes in epithelium, smooth muscle, and mucus glands, and cytologic changes in BAL fluid, all induced by immune sensitization. Our data suggest that chronic immune sensitization per se could be a salient factor in causing many of the changes associated with chronic bronchial asthma.