Activated status of basophils in chronic urticaria leads to interleukin-3 hyper-responsiveness and enhancement of histamine release induced by anti-IgE stimulus

被引:57
作者
Lourenco, F. D. [1 ]
Azor, M. H. [1 ]
Santos, J. C. [1 ]
Prearo, E. [2 ]
Maruta, C. W. [2 ]
Rivitti, E. A. [1 ]
Duarte, A. J. S. [1 ]
Sato, M. N. [1 ]
机构
[1] Univ Sao Paulo, Sch Med, Dept Dermatol, Lab Invest Dermatol & Immunodeficiencies LIM 56, BR-05403000 Sao Paulo, Brazil
[2] Univ Sao Paulo, Sch Med, Hosp Clin, Dermatol Outpatient Clin, BR-05403000 Sao Paulo, Brazil
基金
美国国家科学基金会;
关键词
basophil; CD203c; CD63; chronic urticaria; releasability;
D O I
10.1111/j.1365-2133.2008.08499.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background Basophils and mast cells are the main target cells in chronic idiopathic urticaria (CIU). Besides the basopenia, intrinsic defects of the anti-IgE cross-linking signalling pathway of basophils have been described in CIU. Objectives We sought to investigate the profile of expression of activation markers on basophils of patients with CIU and to explore the effect of interleukin (IL)-3 priming upon anti-IgE cross-linking stimuli through expression of activation markers and basophil histamine releasability. Methods Evaluation of the surface expression of Fc epsilon RI alpha, CD63, CD203c and CD123 on whole blood basophils of patients with CIU undergoing autologous serum skin test (ASST) was performed by flow cytometry. The effect of pretreatment with IL-3 in the anti-IgE response was analysed by the expression of basophil activation markers and histamine release using enzyme-linked immunosorbent assay. Results Blood basophils of patients with CIU were reduced in number and displayed increased surface expression of Fc epsilon RI alpha, which was positively correlated with the IgE serum levels. Upregulation of expression of both surface markers CD203c and CD63 was verified on basophils of patients with CIU, regardless of ASST response. High expression of IL-3 receptor on basophils was detected only in ASST+ patients with CIU. Pretreatment with IL-3 upregulated CD203c expression concomitantly with the excreting function of blood basophils and induced a quick hyper-responsiveness to anti-IgE cross-linking on basophils of patients with CIU compared with healthy controls. Conclusions Basophils of patients with CIU showed an activated profile, possibly due to an in vivo priming. Functionally, basophils have high responsiveness to IL-3 stimulation, thereby suggesting that defects in the signal transduction pathway after IgE cross-linking stimuli are recoverable in subjects with chronic urticaria.
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收藏
页码:979 / 986
页数:8
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