Aspirin-like drugs prime human T cells. Modulation of intracellular calcium concentrations.
Aspirin-like drugs prime human T cells. Modulation of intracellular calcium concentrations.
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DOI：
10.4049/jimmunol.146.8.2553
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发表时间：
1991-04
影响因子：
4.4
通讯作者：
Eliezer Flescher;Donna Fossum;Patrick J. Gray;Gabriel Fernandes;Michael J.K. Harper;Norman Talal
中科院分区：
文献类型：
--
作者：
Eliezer Flescher;Donna Fossum;Patrick J. Gray;Gabriel Fernandes;Michael J.K. Harper;Norman Talal
阿司匹林类药物(ALD)通过抑制单核细胞PG的产生来促进T细胞的增殖。正常人的T细胞不会产生任何二十烷类化合物。因此，我们研究了ALD是否会直接影响纯化的T细胞。我们发现，在没有单核细胞的情况下，ALD能促进T细胞的增殖和IL-2的产生。这种作用不依赖于花生四烯酸代谢，因为没有脂氧合酶产物，在T细胞培养中只检测到非抑制水平的环氧合酶产物。ALD效应的几种可能机制被排除，包括1)促进有丝分裂原结合，2)诱导细胞表面的激活标志(IL-2R，转铁蛋白受体，人类白细胞抗原DR)，3)下调抑制细胞。ALD引起[Ca~(2+)]i升高，这似乎反映了细胞外环境中的Ca~(2+)内流，且在CD_4~+细胞中更为明显。细胞内钙离子水平的上升，被认为是T细胞激活所必需的第二信使，可能为这些细胞对有丝分裂原的增强反应做好准备。此外，ALD增加了T细胞膜的流动性，但只有在高于促进增殖的浓度时才会增加。ALD对T细胞的药理作用可能为这些药物提供了一种新的免疫增强潜力，并可能对免疫抑制的个体具有治疗作用。
Aspirin-like drugs (ALD) enhance T cell proliferation by suppressing PG production in monocytes. Normal human T cells do not produce any eicosanoids. Therefore we studied whether ALD would affect purified T cells directly. We found that ALD enhanced the proliferation and IL-2 production of T cells in the absence of monocytes. This effect did not depend on arachidonic acid metabolism as no lipoxygenase products and only nonsuppressive levels of cyclooxygenase products were detected in T cell cultures. Several possible mechanisms of the ALD effect were ruled out including 1) enhanced mitogen binding, 2) induction of activation markers (IL-2R, transferrin receptor, HLA-DR) on the cell surface, 3) down-regulation of suppressor cells. ALD caused a rise in [Ca2+]i which appeared to reflect an influx of Ca2+ from the extracellular milieu and was more pronounced in CD4+ cells. The rise in intracellular levels of Ca2+, that is considered a necessary second messenger for T cell activation, may prime these cells for an enhanced response to mitogens. In addition, ALD increased T cell membrane fluidity but only at higher concentrations than those found to enhance proliferation. The pharmacologic effect of ALD on T cells presents a possible new immunoenhancing potential of these drugs and may have therapeutic use in immunosuppressed individuals.