ANTIALLERGIC PROPERTIES OF CYCLOSPORINE-A - INHIBITION OF MEDIATOR RELEASE FROM HUMAN BASOPHILS AND RAT BASOPHILIC LEUKEMIA-CELLS (RBL-2H3)

被引:14
作者
EZEAMUZIE, CI
ASSEM, ESK
机构
[1] UNIV LONDON UNIV COLL,DEPT PHARMACOL,GOWER ST,LONDON WC1E 6BT,ENGLAND
[2] UNIV PORT HARCOURT,COLL HLTH SCI,DEPT PHARMACOL,PORT HARCOURT,NIGERIA
来源
IMMUNOPHARMACOLOGY | 1990年 / 20卷 / 01期
关键词
Binding; Calcium; Cyclosporin A; Histamine; Human basophil; Leukotriene; Mediator release; Rat basophil;
D O I
10.1016/0162-3109(90)90005-Y
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In vitro the immonosuppressive drug cyclosporin A (CS-A) strongly inhibited histamine release from human basophils (HB) and the rat basophilic leukemia cell line (RBL) 2H3. It also inhibited leukotriene release from HB. In HB the IC50 values for inhibition of histamine release induced by Con A, anti-IgE, calcium ionophore A23187 and antigen (mite) were 0.03, 0.12, 0.36 and 2.0 μM, respectively. In fact, these figures underestimate the potency of CS-A, since studies with 3H-CS-A showed substantial adsorption to plastic experimental wares which was inversely proportional to drug concentration. With anti-IgE and A23187, the drug acted promptly when added at the same time as the inducers but, with antigen, inhibition increased with time of pre-incubation. Washing of HB after pre-incubation with CS-A did not remove the drug effect. Inhibition of histamine release was abolished by Ca2+ excess (5 mM). For TPA-induced release, the drug inhibited the Ca2+-dependent but not the Ca2+-independent component. In Ca2+-free conditions, ionophore A23187, which caused little or no histamine release on its own, was able to synergize with TPA in causing release, apparently by mobilizing intracellular Ca2+. CS-A blocked the synergism but not the original TPA effect. CS-A was compared with the calmodulin inhibitors, W7, TFP and ABCNS; all inhibited histamine release. CS-A also potently inhibited IgE-mediated histamine release from RBL-2H3 cells, without affecting their growth or viability. © 1990.
引用
收藏
页码:31 / 43
页数:13
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