Schreiber S, Blum J S, Stenson W F, MacDermott R P, Stahl P D, Teitelbaum S L, Perkins S L
Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO.
Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1616-20. doi: 10.1073/pnas.88.5.1616.
The macrophage mannose receptor, a 172-kDa lineage-specific glycoprotein, partakes in nonopsonin-mediated phagocytosis by recognition of terminal mannose residues on targeted particles. Because appearance of the receptor progresses with monocyte/macrophage differentiation, its expression is indicative of the maturational state of the cell. Monomeric IgG2a and IgG2b up-regulate mannose-receptor surface expression and biosynthesis by murine bone-marrow macrophage precursors as much as 7- to 12-fold in a dose-dependent manner. IgG2a accelerates macrophage mannose-receptor expression by several days during in vitro bone-marrow differentiation; however, treated and control cells ultimately express equivalent levels of receptor. Moreover, the effect is independent of cell cycle or ambient levels of colony-stimulating factor 1. The coinduction of another maturation-dependent lineage-specific antigen, F4/80, and the fact that macrophage precursors respond to IgG2a only within the first day of culture, indicate that the targeted cell is an early myelomonocytic precursor, responsive only during a short, early developmental window. The effect is specific for immunoglobulin molecules of the IgG2a and IgG2b subclasses and probably involves an Fc gamma-receptor signal-transduction pathway but not macrophage priming or activation. Most importantly, a paracrine mechanism of immunoglobulin-mediated bone-marrow macrophage differentiation is suggested by experiments in which basal levels of mannose-receptor expression are reduced by continual removal of B-cell-generated IgG from marrow cultures. Thus, IgG2a and IgG2b prompt mannose-receptor synthesis and bone-marrow macrophage differentiation and may, therefore, play a role in the regulation of macrophage differentiation in host defense.
巨噬细胞甘露糖受体是一种172 kDa的谱系特异性糖蛋白，通过识别靶颗粒上的末端甘露糖残基参与非调理素介导的吞噬作用。由于该受体的出现随着单核细胞/巨噬细胞的分化而进展，其表达可指示细胞的成熟状态。单体IgG2a和IgG2b可上调小鼠骨髓巨噬细胞前体的甘露糖受体表面表达和生物合成，呈剂量依赖性，上调幅度可达7至12倍。在体外骨髓分化过程中，IgG2a可使巨噬细胞甘露糖受体的表达提前数天加速；然而，处理组和对照组细胞最终表达的受体水平相当。此外，该效应与细胞周期或集落刺激因子1的环境水平无关。另一种成熟依赖性谱系特异性抗原F4/80的共同诱导，以及巨噬细胞前体仅在培养的第一天对IgG2a有反应这一事实，表明靶细胞是早期骨髓单核细胞前体，仅在短暂的早期发育窗口期有反应。该效应对IgG2a和IgG2b亚类的免疫球蛋白分子具有特异性，可能涉及Fcγ受体信号转导途径，但与巨噬细胞的启动或激活无关。最重要的是，在骨髓培养物中持续去除B细胞产生的IgG可降低甘露糖受体表达的基础水平，这一实验提示了免疫球蛋白介导的骨髓巨噬细胞分化的旁分泌机制。因此，IgG2a和IgG2b可促进甘露糖受体的合成和骨髓巨噬细胞的分化，因此可能在宿主防御中巨噬细胞分化的调节中发挥作用。
