Genetic analysis of the role of cAMP in mediating effects of interferon.
Genetic analysis of the role of cAMP in mediating effects of interferon.
复制标题
cAMP 在干扰素介导作用中的遗传分析。
DOI：
10.1073/pnas.79.6.1879
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发表时间：
1982
影响因子：
11.1
通讯作者：
Bloom,BR
中科院分区：
文献类型：
--
作者：
Schneck,J;Rager-Zisman,B;Rosen,OM;Bloom,BR
在克隆的巨噬细胞样细胞系J774.2及其衍生的变异体中，分析了干扰素（IFN）对Fc受体介导的吞噬作用、细胞内cAMP水平、抗病毒活性和生长抑制的影响。纯化的IFN增加了J774.2细胞和cAMP反应性非吞噬细胞变异体中Fc受体介导的吞噬作用，但对cAMP反应性非吞噬细胞变异体没有影响。腺苷酸环化酶缺陷型和cAMP依赖性蛋白激酶缺陷型。在IFN增强吞噬作用的条件下，它增加了细胞内cAMP的水平。亲本细胞对IFN介导的生长抑制高度敏感。相比之下，cAMP依赖性蛋白激酶缺陷型对IFN生长抑制的敏感性仅为1/100。所有测试的细胞系，响应和不响应cAMP，同样保护IFN对水泡性口炎病毒感染，表明抗病毒状态是独立的cAMP。这些结果表明，在转化的巨噬细胞，刺激吞噬和抑制生长的IFN介导的通过细胞内cAMP，而IFN诱导的抗病毒状态是独立的cAMP。
The effects of interferon (IFN) on Fc receptor-mediated phagocytosis, intracellular cAMP levels, antiviral activity, and growth inhibition were analyzed in a cloned macrophage-like cell line, J774.2, and variants derived from it. Purified IFN increased Fc receptor-mediated phagocytosis in J774.2 cells, and in cAMP-responsive nonphagocytic variants but was without effect in cAMP-unresponsive nonphagocytic variants, in adenylate cyclase-deficient variants, and in cAMP-dependent protein kinase-deficient variants. Under conditions in which IFN augmented phagocytosis, it increased intracellular levels of cAMP. Parental cells were highly sensitive to IFN-mediated growth inhibition. In contrast, cAMP-dependent protein kinase-deficient variants were only 1/100th as sensitive to growth inhibition by IFN. All cell lines tested, both responsive and unresponsive to cAMP, were equally protected by IFN against infection with vesicular stomatitis virus, demonstrating that the antiviral state was independent of cAMP. These results indicate that, in transformed macrophages, stimulation of phagocytosis and inhibition of growth by IFN are mediated through intracellular cAMP, whereas the antiviral state induced by IFN is independent of cAMP.