The effect of inhaled leukotriene D-4 and methacholine on sputum cell differentials in asthma
The effect of inhaled leukotriene D-4 and methacholine on sputum cell differentials in asthma
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DOI：
10.1164/ajrccm.155.4.9105062
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发表时间：
1997-04-01
影响因子：
24.7
通讯作者：
Sterk, PJ
中科院分区：
文献类型：
--
作者：
Diamant, Z;Hiltermann, JT;Sterk, PJ
半胱氨酰白三烯LTE（4）已被证明可诱导哮喘患者体内气道嗜酸性粒细胞增多。LTD（4）尚未报告这种现象。因此，我们检测了吸入LTD（4）和对照支气管收缩剂乙酰甲胆碱对12名非吸烟特应性哮喘受试者（3名女性，9名男性;年龄21 - 29岁; FEV（1），74 - 120% pred; PC（20）FEV（1）乙酰甲胆碱< 9.6 mg/ml）高渗盐水诱导的全痰样本中细胞分化的影响。该研究采用交叉、安慰剂对照设计，包括间隔大于或等于1周的4天。在每个随机研究日，受试者吸入5个连续剂量的LTD（4）（平均累积浓度：95.7 μ M）或乙酰甲胆碱（平均累积浓度：542 mM）或5个剂量的各自的稀释剂（PBS/乙醇或PBS）。用FEV（1）测定气道反应，然后在激发后4 h用4.5%NaCl诱导痰。在编码的细胞离心涂片上对炎性细胞（大于或等于250）计数两次，并表示为非鳞状细胞的百分比。LTD（4）（平均+/- SEM，下降49.5 +/- 4.4%）和乙酰甲胆碱（平均+/-SEM，下降55.9 +/- 3.4%）之间FEV（1）较基线的最大百分比下降无显著差异（p = 0.11）。LTD（4）与其稀释液相比，诱导痰嗜酸性粒细胞百分比显著增加（平均值+/- SD，分别为26.6 +/- 21.3%和10.2 +/-8.8%; p = 0.025），而乙酰甲胆碱的类似趋势未能达到显著性（平均值+/- SD，分别为19.1 +/- 22.9%和7.8 +/-5.8%; p = 0.11）。LTD（4）和乙酰甲胆碱组之间痰嗜酸性粒细胞百分比的变化无显著差异（平均差异+/- SD，7.5 +/- 12.5%嗜酸性粒细胞; p = 0.09）。我们的结论是LTD（4）可诱导哮喘患者吸入后4小时痰液中嗜酸性粒细胞增多。我们的数据表明LTD（4）可能通过直接或间接的趋化特性将嗜酸性粒细胞募集到哮喘患者体内的气道中，而不能排除剧烈气道狭窄本身的额外作用。
The cysteinyl leukotriene LTE(4) has been shown to induce airway eosinophilia in asthmatics in vivo. This phenomenon has not yet been reported for LTD(4). Hence, we examined the effect of inhaled LTD(4) and a control bronchoconstrictor agent, methacholine, on cell differentials in hypertonic saline-induced whole sputum samples of 12 nonsmoking atopic asthmatic subjects (three women, nine men; 21 to 29 yr of age; FEV(1), 74 to 120% pred; PC(20)FEV(1) methacholine < 9.6 mg/ml). The study had a crossover, placebo-controlled design consisting of 4 d separated by greater than or equal to 1 wk. On each randomized study day, the subjects inhaled five serial doses of either LTD(4) (mean cumulative concentration: 95.7 mu M) or methacholine (mean cumulative concentration: 542 mM) or five doses of their respective diluents (PBS/ethanol or PBS). The airway response was measured by FEV(1), followed by sputum induction with 4.5% NaCl, 4 h postchallenge. Inflammatory cells (greater than or equal to 250) were counted twice on coded cytospins and expressed as percentages of nonsquamous cells. There was no significant difference in the maximal percent fall in FEV(1) from baseline between LTD(4) (mean +/- SEM, 49.5 +/- 4.4% fall) and methacholine (mean +/- SEM, 55.9 +/- 3.4% fall) (p = 0.11). LTD(4) induced a significant increase in the percentage of sputum eosinophils as compared with its diluent (mean +/- SD, 26.6 +/- 21.3% and 10.2 +/- 8.8%, respectively; p = 0.025), whereas a similar trend for methacholine failed to reach significance (mean +/- SD, 19.1 +/- 22.9% and 7.8 +/- 5.8%, respectively; p = 0.11). There was no significant difference in the changes in the percentage of sputum eosinophils between LTD(4) and methacholine (mean difference +/- SD, 7.5 +/- 12.5% eosinophils; p = 0.09). We conclude that LTD(4) induces eosinophilia in sputum of asthmatic subjects 4 h after inhalation. Our data suggest that LTD(4) recruits eosinophils into the airways of asthmatics in vivo, possibly by virtue of direct or indirect chemotactic properties, whereas an additional effect of vigourous airway narrowing per se cannot be excluded.