Cowan H B, Vick S, Conary J T, Shepherd V L
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37203.
Arch Biochem Biophys. 1992 Jul;296(1):314-20. doi: 10.1016/0003-9861(92)90578-k.
The macrophage mannose receptor is highly susceptible to modulation by a variety of inflammatory and anti-inflammatory agents. Previous studies have demonstrated that mannose receptor activity is dramatically enhanced in rat bone marrow macrophages following treatment with dexamethasone. In the present study we have investigated potential mechanisms that might be involved in this up-regulation. Uptake of ligands by the mannose receptor was increased 2.5-fold in a dose- and time-dependent manner. Maximal stimulation was seen following treatment of macrophages with 0.1-1.0 microgram/ml of dexamethasone for 24-48 h. Dexamethasone treatment increased both the number of cell surface binding sites and total cellular binding activity to 250% of control levels. In addition, total receptor protein as measured by immunoprecipitation was increased 2.5-fold. Neither the maturation rate nor the turnover rate of the protein was altered by dexamethasone treatment. Using an oligonucleotide probe derived from sequence data from the cloned human receptor cDNA, we investigated the effect of dexamethasone on the expression of mannose receptor mRNA. Following incubation with dexamethasone for 12-24 h, the level of mRNA was significantly increased. These results demonstrate that dexamethasone treatment of rat bone marrow macrophages induces synthesis of new receptor protein through an increase in the level of mannose receptor mRNA.
巨噬细胞甘露糖受体极易受到多种炎性和抗炎性因子的调节。先前的研究表明，用 dexamethasone 处理大鼠骨髓巨噬细胞后，甘露糖受体活性显著增强。在本研究中，我们研究了可能参与这种上调的潜在机制。甘露糖受体对配体的摄取以剂量和时间依赖性方式增加了 2.5 倍。在用 0.1 - 1.0 微克/毫升的 dexamethasone 处理巨噬细胞 24 - 48 小时后，观察到最大刺激作用。Dexamethasone 处理使细胞表面结合位点的数量和总细胞结合活性均增加至对照水平的 250%。此外，通过免疫沉淀法测定的总受体蛋白增加了 2.5 倍。Dexamethasone 处理并未改变蛋白质的成熟率或周转率。使用从克隆的人受体 cDNA 的序列数据衍生而来的寡核苷酸探针，我们研究了 dexamethasone 对甘露糖受体 mRNA 表达的影响。在用 dexamethasone 孵育 12 - 24 小时后，mRNA 水平显著增加。这些结果表明，dexamethasone 处理大鼠骨髓巨噬细胞通过增加甘露糖受体 mRNA 的水平诱导新受体蛋白的合成。
