Comber P G, Rossman M D, Rappaport E F, Chien P, Hogarth P M, Schreiber A D
University of Pennsylvania School of Medicine, Philadelphia.
Cell Immunol. 1989 Dec;124(2):292-307. doi: 10.1016/0008-8749(89)90132-9.
Human monocytes and macrophages express three different classes of cell surface receptors for the Fc portion of IgG, Fc gamma RI (CD64), Gc gamma RII (CD32), and Fc gamma RIII (CD16). We utilized a cDNA probe for Fc gamma RII to examine the modulation of Fc gamma RII mRNA by dexamethasone, a synthetic glucocorticoid, and interferon-gamma. We also determined the changes in the expression of both Fc gamma RI and Fc gamma RII protein following treatment with these agents by flow cytometry. In studies performed with the monocyte-like cell line. U937, Northern blot analysis revealed that cells treated with interferon-gamma showed a 2.5-fold increase in Fc gamma RII mRNA levels that was maximal at 14 hr and declined to 1.4-fold over baseline by 48 hr of incubation. Treatment of U937 cells with dexamethasone did not significantly change the level of Fc gamma RII transcripts, but was able to inhibit by up to 50% the increase seen following interferon-gamma treatment. The expression of Fc gamma RII protein on U937 cells was increased 56-72% after 16-24 hr of interferon-gamma treatment, but was only 18% over baseline after 48 hr of incubation. Treatment with dexamethasone caused a small, but significant, decrease in Fc gamma RII protein, and inhibited by 20-60% the induction of Fc gamma RII by interferon-gamma. The modulation by dexamethasone and interferon-gamma of Fc gamma RI protein expression on U937 cells was markedly different from that of Fc gamma RII in both magnitude and kinetics. Interferon-gamma treatment increased Fc gamma RI expression by 240% at 16 hr, and Fc gamma RI remained elevated through 48 hr. Treatment with dexamethasone decreased Fc gamma RI expression by 39%, and also inhibited by 40% the increase induced by interferon-gamma. In contrast to the findings with U937 cells, dexamethasone and/or interferon-gamma treatment had no significant effect on Fc gamma RII mRNA levels or protein expression in monocytes. However, interferon-gamma treatment increased Fc gamma RI expression on monocytes, and this increase was further augmented by treatment with dexamethasone. These data indicate that the modulation of Fc gamma RII on U937 cells is at least in part due to changes in steady state levels of Fc gamma RII mRNA. The difference between the magnitude of the changes in Fc gamma RII mRNA and protein suggests that some translational or post-translational control is involved in regulating the expression of Fc gamma RII.(ABSTRACT TRUNCATED AT 400 WORDS)
人类单核细胞和巨噬细胞表达三类不同的针对IgG Fc部分的细胞表面受体，即FcγRI（CD64）、FcγRII（CD32）和FcγRIII（CD16）。我们利用FcγRII的cDNA探针来检测地塞米松（一种合成糖皮质激素）和干扰素-γ对FcγRII mRNA的调节作用。我们还通过流式细胞术确定了用这些试剂处理后FcγRI和FcγRII蛋白表达的变化。在用单核细胞样细胞系U937进行的研究中，Northern印迹分析显示，用干扰素-γ处理的细胞FcγRII mRNA水平增加了2.5倍，在14小时时达到最大值，培养48小时后降至比基线高1.4倍。用地塞米松处理U937细胞并没有显著改变FcγRII转录本的水平，但能够抑制高达50%的干扰素-γ处理后出现的增加。干扰素-γ处理16 - 24小时后，U937细胞上FcγRII蛋白的表达增加了56 - 72%，但培养48小时后仅比基线高18%。用地塞米松处理导致FcγRII蛋白有小幅但显著的下降，并抑制了干扰素-γ对FcγRII的诱导作用的20 - 60%。地塞米松和干扰素-γ对U937细胞上FcγRI蛋白表达的调节在幅度和动力学上与FcγRII明显不同。干扰素-γ处理在16小时时使FcγRI表达增加了240%，并且FcγRI在48小时内一直保持升高。用地塞米松处理使FcγRI表达下降了39%，并抑制了干扰素-γ诱导的增加的40%。与U937细胞的结果相反，地塞米松和/或干扰素-γ处理对单核细胞中FcγRII mRNA水平或蛋白表达没有显著影响。然而，干扰素-γ处理增加了单核细胞上FcγRI的表达，并且地塞米松处理进一步增强了这种增加。这些数据表明，U937细胞上FcγRII的调节至少部分是由于FcγRII mRNA稳态水平的变化。FcγRII mRNA和蛋白变化幅度的差异表明，一些翻译或翻译后控制参与了FcγRII表达的调节。（摘要截短至400字）
