Shepherd V L, Konish M G, Stahl P
J Biol Chem. 1985 Jan 10;260(1):160-4.
Macrophages express a mannose-specific pinocytosis receptor that binds and internalizes lysosomal hydrolases. Treatment of rat bone marrow-derived macrophages with dexamethasone resulted in a concentration- and time-dependent increase in mannose-receptor activity. The dexamethasone effect was maximal at 24 h. Half-maximal effects were observed at a dexamethasone concentration of 2.5 X 10(-9) M. With 125I-beta-glucuronidase as ligand, a 2.5-fold increase in uptake rate was observed in dexamethasone-treated cells, with no change in Kuptake (2.5 X 10(-7) M beta-glucuronidase). Cell surface binding (4 degrees C) was elevated 2.6-fold following dexamethasone treatment. The increase in ligand binding appeared to be due to an increase in number of sites with no change in affinity. Cycloheximide suppressed the dexamethasone-mediated rise in receptor number, while cycloheximide alone had little effect on receptor activity over 16 h. These results suggest that dexamethasone stimulates synthesis of mannose receptors in macrophages. Extracellular accumulation of hexosaminidase was sharply reduced by dexamethasone treatment, and corresponded with the rise in mannose-receptor activity. Extracellular levels of hexosaminidase from untreated macrophages were modestly increased by the presence of mannan, while the extracellular activity from dexamethasone-treated cells was increased significantly by mannan. Extracellular hexosaminidase, released from zymosan-treated macrophages, was dramatically reduced by dexamethasone pretreatment. Enzyme released from zymosan-stimulated macrophages was efficiently endocytosed by dexamethasone-treated cells in co-culture experiments, and this endocytosis was blocked by the addition of mannan. These results suggest that the mannose receptor of macrophages may play a role in regulating extracellular levels of lysosomal enzymes via a secretion-recapture mechanism.
巨噬细胞表达一种甘露糖特异性的胞饮受体，该受体可结合并内化溶酶体水解酶。用地塞米松处理大鼠骨髓来源的巨噬细胞，可导致甘露糖受体活性呈浓度和时间依赖性增加。地塞米松的作用在24小时时达到最大。在2.5×10⁻⁹ M的地塞米松浓度下观察到半数最大效应。以¹²⁵I-β-葡萄糖醛酸酶作为配体，在地塞米松处理的细胞中观察到摄取率增加了2.5倍，而摄取常数（2.5×10⁻⁷ M β-葡萄糖醛酸酶）没有变化。地塞米松处理后，细胞表面结合（4℃）增加了2.6倍。配体结合的增加似乎是由于位点数量增加而亲和力不变。放线菌酮抑制了地塞米松介导的受体数量增加，而单独使用放线菌酮在16小时内对受体活性几乎没有影响。这些结果表明地塞米松刺激巨噬细胞中甘露糖受体的合成。地塞米松处理可使己糖胺酶的细胞外积累急剧减少，这与甘露糖受体活性的增加相对应。未处理的巨噬细胞的细胞外己糖胺酶水平因甘露聚糖的存在而适度增加，而地塞米松处理细胞的细胞外活性则因甘露聚糖而显著增加。经酵母聚糖处理的巨噬细胞释放的细胞外己糖胺酶，用地塞米松预处理后显著降低。在共培养实验中，酵母聚糖刺激的巨噬细胞释放的酶被地塞米松处理的细胞有效内吞，并且这种内吞作用被甘露聚糖的添加所阻断。这些结果表明巨噬细胞的甘露糖受体可能通过分泌-再捕获机制在调节溶酶体酶的细胞外水平中发挥作用。
