Schneck J, Rager-Zisman B, Rosen O M, Bloom B R
Proc Natl Acad Sci U S A. 1982 Mar;79(6):1879-83. doi: 10.1073/pnas.79.6.1879.
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.
在一个克隆的巨噬细胞样细胞系J774.2及其衍生变体中，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细胞以及对cAMP有反应的非吞噬性变体中的Fc受体介导的吞噬作用，但对cAMP无反应的非吞噬性变体、腺苷酸环化酶缺陷变体和cAMP依赖性蛋白激酶缺陷变体没有影响。在IFN增强吞噬作用的条件下，它增加了细胞内cAMP水平。亲代细胞对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变体对IFN介导的生长抑制的敏感性仅为亲代细胞的1/100。所有测试的细胞系，无论对cAMP有反应还是无反应，都同样受到IFN的保护而免受水疱性口炎病毒感染，这表明抗病毒状态与cAMP无关。这些结果表明，在转化的巨噬细胞中，IFN对吞噬作用的刺激和对生长的抑制是通过细胞内cAMP介导的，而IFN诱导的抗病毒状态与cAMP无关。
