Munn D H, Bree A G, Beall A C, Kaviani M D, Sabio H, Schaub R G, Alpaugh R K, Weiner L M, Goldman S J
Division of Pediatric Hematology-Oncology, Medical College of Georgia, Augusta, USA.
Blood. 1996 Aug 15;88(4):1215-24.
The CD16 receptor (Fc gamma R-III) is found on many tissue macrophages (M phi s), but its expression on circulating monocytes is restricted to a small, phenotypically distinct subset. The number of these CD16+ monocytes may be markedly increased in response to sepsis, human immunodeficiency virus infection, or metastatic malignancy. We have recently shown that the CD16+ monocyte population is selectively expanded by administration of recombinant human macrophage colony-stimulating factor (rhM-CSF). In the current study, we used the highly rhM-CSF-responsive cynomolgus primate model to further characterize this novel monocyte population. Animals treated with rhM-CSF underwent a progressive and essentially complete conversion to the CD16+ monocyte phenotype, with up to a 50-fold increase in the number of CD16+ cells. This increase was paralleled by the emergence of a population of circulating cells that morphologically resembled large granular lymphocytes (LGLs). However, quantitatively, this population corresponded closely to the number of CD16+ monocytes, and fluorescence-activated cell sorting (FACS) confirmed that they were the same. In addition to their LGL-like morphology, many rhM-CSF-induced CD16+ monocytes showed a pattern of size, granularity, and quantitative cell surface marker expression that closely resembled the pretreatment LGL/natural killer (NK) cell population but that did not resemble the pretreatment monocyte population. However, rhM-CSF-induced CD16+ monocytes could be distinguished from LGL/ NK cells by fact that they all expressed cell surface receptors for rhM-CSF, and many of them showed reduced but detectable phagocytic and respiratory burst activity. Studies of human subjects treated with rhM-CSF also showed an analogous population of "LGL-appearing" CD16+ mononuclear cells. Thus, our studies reveal a previously unsuspected ability of cells in the monocyte lineage to adopt a phenotype similar to that of LGL/NK cells. The extent of this phenotypic convergence suggests that the two lineages retain access to elements of a similar developmental pathway.
CD16受体（FcγR-III）存在于许多组织巨噬细胞上，但它在循环单核细胞上的表达仅限于一小部分表型不同的亚群。这些CD16+单核细胞的数量在败血症、人类免疫缺陷病毒感染或转移性恶性肿瘤的情况下可能会显著增加。我们最近发现，通过给予重组人巨噬细胞集落刺激因子（rhM-CSF），CD16+单核细胞群体可被选择性扩增。在当前研究中，我们使用高度rhM-CSF反应性的食蟹猴灵长类动物模型来进一步表征这个新的单核细胞群体。用rhM-CSF治疗的动物逐渐并基本完全转变为CD16+单核细胞表型，CD16+细胞数量增加了50倍。这种增加伴随着一群形态上类似于大颗粒淋巴细胞（LGL）的循环细胞的出现。然而，从数量上看，这群细胞与CD16+单核细胞的数量密切对应，荧光激活细胞分选（FACS）证实它们是相同的。除了具有LGL样形态外，许多rhM-CSF诱导的CD16+单核细胞在大小、颗粒度和细胞表面标志物定量表达模式上与预处理的LGL/自然杀伤（NK）细胞群体非常相似，但与预处理的单核细胞群体不同。然而，rhM-CSF诱导的CD16+单核细胞可以与LGL/NK细胞区分开来，因为它们都表达rhM-CSF的细胞表面受体，并且其中许多细胞的吞噬和呼吸爆发活性降低但仍可检测到。对接受rhM-CSF治疗的人类受试者的研究也显示出类似的“LGL样”CD16+单核细胞群体。因此，我们的研究揭示了单核细胞谱系中的细胞以前未被怀疑的能够采用类似于LGL/NK细胞表型的能力。这种表型趋同的程度表明这两个谱系保留了对相似发育途径元件的 access。 （最后一句“access”在原文语境中不太明确准确意思，翻译可能不太精准）
