Phosphodiesterase inhibition by Ro 20-1724 reduces hyper-IgE synthesis by atopic dermatitis cells in vitro.
Phosphodiesterase inhibition by Ro 20-1724 reduces hyper-IgE synthesis by atopic dermatitis cells in vitro.
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Ro 20-1724 抑制磷酸二酯酶可减少体外特应性皮炎细胞的高 IgE 合成。
DOI：
10.1111/1523-1747.ep12272486
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Hanifin,JM
中科院分区：
文献类型：
--
作者：
Cooper,KD;Kang,K;Chan,SC;Hanifin,JM
特应性皮炎患者外周血单核白细胞（MNL）在体外自发产生大量IgE。这些细胞还显示cAMP磷酸二酯酶（PDE）水平显著升高，这可能是观察到的异常cAMP反应性的原因。用不同浓度的cAMP PDE抑制剂Ro 20-1724治疗特应性皮炎MNL，导致IgE合成量逐渐减少，在10- 4 M和10- 5 M浓度下具有统计学显著性。PDE抑制和IgE合成抑制之间密切相关，r = 0.93，p <0.05。为了确定药物的细胞靶点，我们使用了针对MNL亚群（Lyt 3，OKT 8，OKT 4，单核细胞-骨髓）的单克隆抗体，采用改良的“淘选”方法进行纯化亚群的实验。与未经处理的子集，OKT 4阳性细胞的去除显着降低IgE的合成，再添加OKT 4阳性细胞增强IgE的合成。OKT 8细胞和单核细胞不影响IgE的合成。用Ho 20-1724预处理T细胞耗尽的MNL导致比在与相互未处理的亚群重组和随后的培养物之前预处理T富集的细胞显著更多的IgE合成抑制。类似地，单核细胞耗竭细胞的预处理导致比重组和培养之前单核细胞富集细胞的预处理显著更多的IgE合成抑制。大部分效应似乎是通过对B细胞的直接效应介导的。然而，通过预处理富含T细胞也实现了IgE合成的一些抑制。由于分离的抑制/细胞毒性或辅助/诱导T细胞亚群的预处理不能产生与未分级T细胞相同程度的抑制，因此在这方面可能涉及T-T相互作用。咪唑啉酮衍生物Ro 20-1724显著且一致地抑制来自特应性皮炎患者的MNL的升高的cAMP磷酸二酯酶活性和升高的自发IgE合成。这些发现证实了cAMP PDE水平与体外IgE合成之间的联系。
Peripheral blood mononuclear leukocytes (MNL) from patients with atopic dermatitis spontaneously produce large amounts of IgE in vitro. These cells also show markedly elevated levels of cAMP phosphodiesterase (PDE) which may be responsible for the observed abnormal cAMP responsiveness. Treatment of atopic dermatitis MNL with varying concentrations of the cAMP PDE inhibitor Ro 20-1724 resulted in progressively decreasing amounts of IgE synthesis, statistically significant at the 10-4M and 10-5M concentrations. There was a close correlation between PDE inhibition and inhibition of IgE synthesis, r = 0.93, p <0.05. To define the cellular target of the drug, we used monoclonal antibodies directed toward MNL subsets (Lyt 3, OKT8, OKT4, monocyte-myeloid) in a modified “panning” method to perform experiments with purified subsets. With untreated subsets, removal of OKT4-positive cells significantly reduced IgE synthesis; readdition of OKT4-positive cells enhanced IgE synthesis. OKT8 cells and monocytes did not affect IgE synthesis. Pretreatment of T cell-depleted MNL with Ho 20-1724 resulted in significantly more inhibition of IgE synthesis than did pretreatment of T enriched cells prior to recombination with the reciprocal untreated subset and subsequent culture. Similarly, pretreatment of monocyte-depleted cells resulted in significantly more inhibition of IgE synthesis than pretreatment of monocyte-enriched cells prior to recombination and culture. The majority of the effect appeared to be mediated by a direct effect on the B cells. However, some inhibition of IgE synthesis was also achieved through pretreatment of T enriched cells. Since pretreatment of isolated suppressor/cytotoxic or helper/inducer T-cell subsets did not give the same degree of inhibition as with unfractionated T cells, a T-T interaction may be involved in this aspect. The imidazolidinone derivative, Ro 20-1724, significantly and consistently inhibited both the elevated cAMP phophodiesterase activity and the elevated spontaneous IgE synthesis of MNL from patients with atopic dermatitis. These findings demonstrate a previously indescribed link between cAMP PDE levels and in vitro IgE synthesis.
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DOI：
10.1159/000232872
发表时间：
1981
期刊：
International archives of allergy and applied immunology
影响因子：
--
作者：
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DOI：
10.1016/0091-6749(81)90187-1
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1981
期刊：
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影响因子：
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作者：
A. H. Tjio;W. Hull;G. Gleich
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DOI：
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发表时间：
1978-01-01
影响因子：
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DOI：
10.1016/0090-1229(81)90214-2
发表时间：
1981
期刊：
Clinical immunology and immunopathology
影响因子：
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作者：
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