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哮喘患者和正常受试者支气管肺泡灌洗细胞组胺和前列腺素D2的自发性非特异性释放:奈多罗米钠的作用

Spontaneous and non-specific release of histamine and PGD2 by bronchoalveolar lavage cells from asthmatic and normal subjects: effect of nedocromil sodium.

作者信息

Lebel B, Bousquet J, Chanez P, Barneon G, Morel A, Michel F B, Godard P

机构信息

INSERM U58, Montpellier, France.

出版信息

Clin Allergy. 1988 Nov;18(6):605-13. doi: 10.1111/j.1365-2222.1988.tb02912.x.

Abstract

Mast cells have been implicated in the pathogenesis of allergic asthma but their role in non-allergic asthma remains to be elucidated. The spontaneous and non-specific release of histamine by suboptimal doses of calcium ionophore A23187 was studied in bronchoalveolar lavage cells obtained from nine asthmatic and seven healthy individuals. Bronchoalveolar lavage was performed with saline, and total cells were incubated without any secretagogue (spontaneous histamine release) or after addition of 1.25, 2.5 and 5 microM of A23187 for 30 min (net maximal release). Histamine was titrated by using a very sensitive radioimmunoassay using a monoclonal antibody against acylated histamine. The spontaneous release was similar in asthmatic (20.6 +/- 8.2%) and healthy individuals (17.4 +/- 8.4%). The net maximal release of histamine was significantly greater in asthmatic patients (28.1 +/- 17.4%) than in normal subjects (10.3 +/- 8.9%). The release of histamine was significantly correlated to the release of PGD2 measured by enzyme immunoassay using a polyclonal antibody against methoxamine-PGD2 (Spearman rank test: 0.78, P less than 0.01). In eight subjects, the release of histamine by A23187 was studied in the presence of nedocromil sodium and it was observed that this drug significantly (P less than 0.05) decreased the net maximal release of histamine. This study shows that mast cells from asthmatic individuals have a greater releasability than those of normal subjects.

摘要

肥大细胞与过敏性哮喘的发病机制有关,但其在非过敏性哮喘中的作用仍有待阐明。研究了用次优剂量的钙离子载体A23187从9名哮喘患者和7名健康个体获取的支气管肺泡灌洗细胞中组胺的自发和非特异性释放。用生理盐水进行支气管肺泡灌洗,将总细胞在无任何促分泌剂的情况下孵育(组胺自发释放),或在加入1.25、2.5和5微摩尔/升的A23187后孵育30分钟(净最大释放)。使用抗酰化组胺的单克隆抗体通过非常灵敏的放射免疫测定法滴定组胺。哮喘患者(20.6±8.2%)和健康个体(17.4±8.4%)的组胺自发释放相似。哮喘患者组胺的净最大释放(28.1±17.4%)显著高于正常受试者(10.3±8.9%)。组胺的释放与使用抗甲氧胺-PGD2多克隆抗体通过酶免疫测定法测得的PGD2释放显著相关(Spearman秩检验:0.78,P<0.01)。在8名受试者中,研究了在奈多罗米钠存在下A23187诱导的组胺释放,观察到该药物显著(P<0.05)降低了组胺的净最大释放。这项研究表明,哮喘个体的肥大细胞比正常受试者的肥大细胞具有更高的释放能力。

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