Smith M R, Ramsburg E A, Kung H F, Durum S K
Biological Carcinogenesis and Development Program, DynCorp, Frederick, MD.
J Immunol. 1992 Aug 15;149(4):1304-10.
Macrophages are activated by a variety of microbial and cytokine stimuli. One feature of activation is the induction of class II Ag (Ia) on the cell surface. To understand the intracellular events that occur during activation, we investigated various agents with intracellular activities, and examined their effects on the induction of Ia. We first noted that several agents that activate protein kinase C (PKC) induced Ia, and that several inhibitors of PKC inhibited Ia induction by IFN-gamma. To directly test whether PKC induced Ia, we microinjected normal peritoneal macrophages with this enzyme and other intracellular mediators, then examined Ia expression. We observed that injection of PKC itself, or of other intracellular proteins thought to participate in the PKC pathway (Ras or phospholipase C gamma) strongly induced Ia expression. The Ia-inducing activity of transforming Ras protein was blocked by kinase inhibitor treatment of cells, suggesting that Ras signal transduction requires kinase activity. On the other hand, components of the protein kinase A pathway (phospholipase A2 and protein kinase A itself) did not induce Ia. Thus, the PKC pathway can control expression of macrophage surface Ia, possibly by regulating the genes of the MHC, and may play many other roles in the activation of macrophages.
巨噬细胞可被多种微生物和细胞因子刺激激活。激活的一个特征是在细胞表面诱导II类抗原（Ia）。为了解激活过程中发生的细胞内事件，我们研究了具有细胞内活性的各种因子，并检测了它们对Ia诱导的影响。我们首先注意到，几种激活蛋白激酶C（PKC）的因子可诱导Ia，而几种PKC抑制剂可抑制IFN-γ诱导的Ia。为直接检测PKC是否诱导Ia，我们向正常腹腔巨噬细胞显微注射该酶及其他细胞内介质，然后检测Ia表达。我们观察到，注射PKC本身或其他被认为参与PKC途径的细胞内蛋白（Ras或磷脂酶Cγ）可强烈诱导Ia表达。用激酶抑制剂处理细胞可阻断转化Ras蛋白的Ia诱导活性，这表明Ras信号转导需要激酶活性。另一方面，蛋白激酶A途径的成分（磷脂酶A2和蛋白激酶A本身）不会诱导Ia。因此，PKC途径可能通过调节MHC基因来控制巨噬细胞表面Ia的表达，并且可能在巨噬细胞激活中发挥许多其他作用。
