Schreiber S, Perkins S L, Teitelbaum S L, Chappel J, Stahl P D, Blum J S
Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110.
J Immunol. 1993 Nov 1;151(9):4973-81.
The macrophage mannose receptor mediates the clearance of microorganisms and glycoproteins containing terminal mannose oligosaccharides. Cell surface expression of this receptor progresses with macrophage differentiation, and thus may be critical to the scavenger function of tissue and circulating macrophages. Bone marrow macrophages, which were used in this study, differentiate in culture and express functional mannose receptors. The cytokine IFN-gamma triggered activation of these macrophages and down-regulated cell surface expression of the mannose receptor after 48 h. Macrophage activation, as assessed by the generation of superoxide radicals, was inversely correlated with mannose receptor expression. The number of surface receptors was diminished by exposure to IFN-gamma, whereas the binding affinity of the mannose receptor remained unchanged. Treatment with IFN-gamma reduced receptor biosynthesis yet did not alter receptor degradation. Mannose receptor biosynthesis is up-regulated by PG of the E series, and these anti-inflammatory agents reversed the effects of IFN-gamma on receptor expression. Down-regulation of the mannose receptor by IFN-gamma was fully reversible by PGE, indicating that receptor levels are dependent on the functional state of the cell rather than being linked to terminal cell differentiation. The regulation of the receptor by cytokines and anti-inflammatory reagents suggests that the mannose receptor plays a critical role in macrophage scavenger functions and potentially in modulating inflammatory reactions.
巨噬细胞甘露糖受体介导含末端甘露糖寡糖的微生物和糖蛋白的清除。该受体的细胞表面表达随巨噬细胞分化而进展，因此可能对组织巨噬细胞和循环巨噬细胞的清除功能至关重要。本研究中使用的骨髓巨噬细胞在培养中分化并表达功能性甘露糖受体。细胞因子IFN-γ触发这些巨噬细胞的活化，并在48小时后下调甘露糖受体的细胞表面表达。通过超氧自由基生成评估的巨噬细胞活化与甘露糖受体表达呈负相关。暴露于IFN-γ会减少表面受体的数量，而甘露糖受体的结合亲和力保持不变。IFN-γ处理会减少受体生物合成，但不会改变受体降解。E系列前列腺素会上调甘露糖受体生物合成，这些抗炎剂可逆转IFN-γ对受体表达的影响。PGE可使IFN-γ对甘露糖受体的下调完全逆转，表明受体水平取决于细胞的功能状态，而非与终末细胞分化相关。细胞因子和抗炎试剂对受体的调节表明，甘露糖受体在巨噬细胞清除功能中以及在调节炎症反应中可能起着关键作用。
