Inhibitability and enhanceability of basophil histamine release in asthmatic and normal subjects.
Inhibitability and enhanceability of basophil histamine release in asthmatic and normal subjects.
复制标题
哮喘和正常受试者中嗜碱性粒细胞组胺释放的抑制性和增强性。
DOI：
10.1159/000233719
复制
发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Lichtenstein,LM
中科院分区：
文献类型：
--
作者：
Peters,SP;Tung,RS;Chatham,M;Bleecker,ER;Lichtenstein,LM
循环中的人类嗜碱性粒细胞含有组胺，一种有效的炎症介质。以前的体外研究表明，组胺的“释放能力”在哮喘患者与正常人不同，但没有评估可能的差异，在免疫药理学控制释放这种介质，这可能会导致这些差异。本研究的目的是研究14例哮喘患者和10例正常人嗜碱性粒细胞组胺释放的免疫药理学控制，其特征是肺功能试验，过敏状态（皮肤试验和血清IgE水平）和非特异性气道反应乙酰甲胆碱和组胺。用抗IgE刺激嗜碱性粒细胞，并研究了H2激动剂二甲双胍和二丁酰环腺苷酸（dbcAMP）的抑制作用，以及5-羟基过氧二十碳四烯酸（5-HPETE）和吲哚美辛对组胺释放调节的增强作用。虽然在这两组中，抗IgE抗体引发的组胺释放百分比没有统计学显著差异，但哮喘受试者（10/10）中5-HPETE对组胺释放的增强作用比对照受试者（6/8）更一致。在哮喘受试者中，使用0.03 µg抗IgE/ml的5-HPETE产生的组胺释放增加百分比平均为3.9 ± 1.3%，使用0.0 µg抗IgE/ml的5-HPETE产生的组胺释放增加百分比平均为4.8 ± 3.2%（p < 0.002，Wilcoxon符号秩检验），在对照受试者中，5-HPETE产生的组胺释放增加百分比平均分别为3.0 ± 4.3%和3.1 ± 5.3%（p > 0.10）。哮喘受试者的嗜碱性粒细胞对0.03 µg/ml抗IgE浓度的dbcAMP抑制作用的敏感性也略高于对照受试者（哮喘受试者的log 10 ID 50 [M] = -3.26 ± 0.33，对照受试者为-2.87 ± 0.43，p < 0.05）。哮喘组与正常对照组之间对二甲双胍的耐受性和对吲哚美辛的增强性无差异。此外，未发现组胺释放的抑制性或增强性与非特异性气道反应性、过敏状态或基线肺功能之间存在相关性。这些结果表明，在哮喘受试者中，嗜碱性粒细胞释放介质的免疫药理学控制机制仅存在细微差异，而所描述的释放性存在更显著的差异。
Circulating human basophils contain histamine, a potent mediator of inflammation. Previous in vitro studies have shown that histamine 'releasability' in asthmatic subjects differs from normal subjects but have not evaluation possible differences in the immunopharmacological control of the release of this mediator which might account for these differences. The purpose of the present study was to examine the immunopharmacologic control of basophil histamine release in 14 asthmatics and 10 normal subjects who were characterized by pulmonary function tests, allergic status (skin tests and serum IgE levels) and nonspecific airways reactivity to methacholine and histamine. Basophils were stimulated with anti-IgE, and the inhibitory effects of the H2agonist, dimaprit, and dibutyryl cyclic AMP (dbcAMP), as well as the enhancing properties of 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and indomethacin on the modulation of histamine release, were investigated. Although no statistically significant differences were seen in the percent histamine release triggered by anti-IgE in these two groups, enhancement of histamine release by 5-HPETE was more consistent in the asthmatic subjects (10 of 10) than in control subjects (6 of 8). The percent increase in histamine release produced by 5-HPETE in asthmatic subjects averaged 3.9 ± 1.3% using 0.03 µg anti-IgE/ml and 4.8 ± 3.2% using 0.0 µg anti IgE/ml (p < 0.002, Wilcoxon's signed rank test), and averaged 3.0 ± 4.3 and 3.1 ± 5.3%, respectively, in control subjects (p > 0.10). Basophils from asthmatic subjects were also slightly more sensitive to inhibition by dbcAMP at an anti-IgE concentration of 0.03 µg/ml than those from control subjects (log10ID50[M] = –3.26 ± 0.33 for asthmatics and –2.87 ± 0.43 for controls, p < 0.05). No differences in inhibitability by dimaprit or enhanceability by indomethacin were found between the asthmatic and normal subjects. In addition, no correlation was found between inhibitability or enhanceability of histamine release and nonspecific airways reactivity, allergic status, or baseline pulmonary function. These results suggest that there are only subtle differences in immunopharmacologic control mechanisms of mediator release from basophils in asthmatic subjects, in contrast to the more marked differences in releasibility described.