Fanger N A, Wardwell K, Shen L, Tedder T F, Guyre P M
Department of Physiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
J Immunol. 1996 Jul 15;157(2):541-8.
Three classes of Fc receptors for IgG, Fc gamma RI (CD64), Fc gamma RII (CD32), and Fc gamma RIII (CD16), are expressed on blood leukocytes. Although Fc gamma R are important phagocytic receptors on phagocytes, most reports suggest that dendritic cells lack Fc gamma R-mediated phagocytosis and express significant levels of only CD32. We now report that phagocytically active forms of both CD64 and CD32 are expressed significantly on at least one subset of human blood dendritic cells. Countercurrent elutriation and magnetic bead selection were used to rapidly enrich subsets of blood dendritic cells (CD33brightCD14-HLA-DRbrightCD83-) and monocytes (CD33brightCD14brightHLA-DRdimCD83-). Upon culture for 2 days, dendritic cells became CD83-positive and markedly increased HLA-DR expression, whereas monocytes did not express CD83 and exhibited reduced levels of HLA-DR. Constitutive CD64 expression was identified on this circulating dendritic cell population, but at a lower level than on monocytes. CD64 expression by dendritic cells and monocytes did not decrease during 2 days in culture, and was up-regulated on both cell types following incubation with IFN-gamma. Freshly isolated blood dendritic cells performed CD64- and CD32-mediated phagocytosis, although at a lower level than monocytes. Dendritic cells generated by culture of adherent mononuclear cells in granulocyte-macrophage CSF and IL-4 also up-regulated CD64 following IFN-gamma stimulation, and mediated CD64-dependent phagocytosis. These results indicate that both CD64 and CD32 expressed on blood dendritic cells may play a role in uptake of foreign particles and macromolecules through a phagocytic mechanism before trafficking to T cell-reactive areas.
血液白细胞上表达三类IgG的Fc受体,即FcγRI(CD64)、FcγRII(CD32)和FcγRIII(CD16)。尽管FcγR是吞噬细胞上重要的吞噬受体,但大多数报告表明,树突状细胞缺乏FcγR介导的吞噬作用,且仅表达显著水平的CD32。我们现在报告,CD64和CD32的吞噬活性形式在至少一部分人血液树突状细胞上有显著表达。采用逆流淘析和磁珠分选法快速富集血液树突状细胞(CD33brightCD14-HLA-DRbrightCD83-)和单核细胞(CD33brightCD14brightHLA-DRdimCD83-)亚群。培养2天后,树突状细胞变为CD83阳性,HLA-DR表达明显增加,而单核细胞不表达CD83,HLA-DR水平降低。在这种循环树突状细胞群体中鉴定出组成性CD64表达,但水平低于单核细胞。树突状细胞和单核细胞的CD64表达在培养2天期间没有降低,并且在与IFN-γ孵育后两种细胞类型上均上调。新鲜分离的血液树突状细胞可进行CD64和CD32介导的吞噬作用,尽管水平低于单核细胞。在粒细胞-巨噬细胞集落刺激因子和IL-4中培养贴壁单核细胞产生的树突状细胞在IFN-γ刺激后也上调CD64,并介导CD64依赖性吞噬作用。这些结果表明,血液树突状细胞上表达的CD64和CD32在转运至T细胞反应区之前,可能通过吞噬机制在摄取外来颗粒和大分子中发挥作用。