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血小板活化因子增强嗜酸性粒细胞IgE受体(FcεR2)的表达及其功能。

Enhancement of the expression of eosinophil IgE receptor (Fc epsilon R2) and its function by platelet-activating factor.

作者信息

Walsh G M, Moqbel R, Nagakura T, Iikura Y, Kay A B

机构信息

Department of Allergy and Clinical Immunology, National Heart and Lung Institute, London, U.K.

出版信息

J Lipid Mediat. 1990;2 Suppl:S177-86.

PMID:1966815
Abstract

Eosinophils possess low-affinity Fc immunoglobulin E (IgE) receptors (Fc epsilon R2). We have compared platelet-activating factor (PAF) with lyso-PAF, leukotriene B4 (LTB4) and histamine for their ability to influence the binding of a native myeloma IgE to normal-density human eosinophils, using flow cytometry and a fluorescein-conjugated anti-IgE polyclonal antibody. Preincubation with PAF gave a dose- and time-dependent increase in IgE binding optimal at 10(-7) M (P less than 0.01) and 30 min respectively. A smaller but significant effect was observed with LTB4 and histamine (optimal at 10(-7) M (P less than 0.01) and 10(-5) M (P less than 0.05) respectively). Diluent alone or lyso-PAF had no effect. These results suggest enhanced expression of Fc epsilon R2 by stimulated eosinophils. Further confirmation of enhancement was obtained using two functional assays, i.e., cytotoxicity and mediator (LTC4) generation. IgE-dependent cytotoxicity against schistosomula of Schistosoma mansoni was enhanced by prior incubation of normal eosinophils with PAF (optimal at 10(-7) M), but not lyso-PAF. No LTC4 was detectable following incubation of unstimulated eosinophils with S. mansoni coated with specific IgE. Preincubation of these cells with PAF (10(-7) M) resulted in the generation of 4.4 pmol of LTC4 per 10(6) cells. Our data demonstrate that normal-density eosinophil Fc epsilon R2 expression can be up-regulated in vitro by PAF and LTB4 and that these changes are accompanied by enhanced functional properties.

摘要

嗜酸性粒细胞具有低亲和力的Fc免疫球蛋白E(IgE)受体(FcεR2)。我们使用流式细胞术和荧光素偶联的抗IgE多克隆抗体,比较了血小板活化因子(PAF)与溶血PAF、白三烯B4(LTB4)和组胺对天然骨髓瘤IgE与正常密度人嗜酸性粒细胞结合的影响能力。用PAF预孵育导致IgE结合呈剂量和时间依赖性增加,分别在10^(-7) M(P<0.01)和30分钟时达到最佳。LTB4和组胺观察到较小但显著的作用(分别在10^(-7) M(P<0.01)和10^(-5) M(P<0.05)时最佳)。单独的稀释剂或溶血PAF没有作用。这些结果表明,受刺激的嗜酸性粒细胞增强了FcεR2的表达。使用两种功能测定,即细胞毒性和介质(LTC4)生成,获得了增强的进一步证实。正常嗜酸性粒细胞与PAF(最佳浓度为10^(-7) M)预孵育可增强对曼氏血吸虫童虫的IgE依赖性细胞毒性,但溶血PAF则无此作用。未刺激的嗜酸性粒细胞与包被有特异性IgE的曼氏血吸虫孵育后未检测到LTC4。这些细胞与PAF(10^(-7) M)预孵育导致每10^6个细胞产生4.4 pmol的LTC4。我们的数据表明,正常密度的嗜酸性粒细胞FcεR2表达在体外可被PAF和LTB4上调,并且这些变化伴随着功能特性的增强。

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