Inhibitability and Enhanceability of Basophil Histamine Release in Asthmatic and Normal Subjects

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Abstract
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 H2 agonist, 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 (log10 ID50 [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.