van Hal P T, Wijkhuijs J M, Mulder P G, Hoogsteden H C
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
Cell Prolif. 1995 Oct;28(10):533-43. doi: 10.1111/j.1365-2184.1995.tb00042.x.
A continuous influx of peripheral blood monocytes (PBM) to the lung is thought to maintain the local population of alveolar macrophages (AM). However, local proliferation of a small subpopulation of AM has been demonstrated in animal studies and in humans. AM exhibit a great heterogeneity with regard to their morphology (cell size, shape of nucleus), immunophenotype (expression of CD14 and RFD9 antigen), and function. Part of this heterogeneity may be explained by the presence of different maturation stages of AM, ranging from small immature, CD14+ RFD9- PBM-like cells to large, CD14- RFD9+ mature AM. These findings prompted us to study whether proliferation of PBM and AM is related to their stage of maturation. The expression of the proliferation marker Ki-67 was studied in AM from both healthy volunteers and patients suffering from sarcoidosis. Using double immunofluorescence staining, we studied proliferation of immature, CD14+ AM, and mature, RFD9+ AM in sarcoidosis, and we compared this with PBM. A significantly larger percentage of AM in general expressed Ki-67 antigen in sarcoidosis (3.0 (median); range 1.1-5.5) as compared with healthy volunteers (0.8; 0.2-1.3). In sarcoidosis, proliferation was observed in both the immature and the mature subpopulation of AM. Proliferating PBM were rarely observed [less than 0.2% of the CD14+ mononuclear cells (MNC)] both in healthy volunteers and sarcoidosis patients. A small subpopulation of PBM showed a weak expression of RFD9 antigen (less than 1% of MNC). Interestingly, proliferation of PBM was concentrated in this subpopulation (15% of the RFD9+ MNC). These data show that even mature AM, which are generally thought to be terminally differentiated cells with little capacity to replicate, are able to proliferate, whereas a relatively very low percentage of their precursors in the blood circulation proliferates. Furthermore, the findings suggest that lung tissue in sarcoidosis creates an environment which promotes proliferation of monocytic cells. Pulmonary alveolar macrophages (AM) were originally recognized as phagocytosing scavenger cells (Ham & Cormack 1979), but presently they are also known to initiate and regulate inflammatory and immunological processes in several lung diseases (Herscowitz 1985, Unanue & Allen 1987, Sibille & Reynolds 1990). AM are thought to represent more mature cells of the mononuclear phagocyte system, and to be derived from peripheral blood monocytes (PBM) (Van Furth 1982, Ginsel 1993). As AM are continuously lost (mainly through a transport from the peripheral airways, via the trachea to the pharynx), the local AM population must be constantly replenished.(ABSTRACT TRUNCATED AT 400 WORDS)
外周血单核细胞（PBM）持续流入肺部被认为可维持肺泡巨噬细胞（AM）的局部数量。然而，在动物研究和人体研究中均已证实，一小部分AM存在局部增殖现象。AM在形态（细胞大小、细胞核形状）、免疫表型（CD14和RFD9抗原的表达）和功能方面表现出很大的异质性。这种异质性的部分原因可能是存在不同成熟阶段的AM，从小的未成熟、CD14 + RFD9 - 的PBM样细胞到大型的、CD14 - RFD9 + 的成熟AM。这些发现促使我们研究PBM和AM的增殖是否与其成熟阶段相关。我们研究了健康志愿者和结节病患者AM中增殖标志物Ki - 67的表达。通过双重免疫荧光染色，我们研究了结节病中未成熟的CD14 + AM和成熟的RFD9 + AM的增殖情况，并将其与PBM进行比较。与健康志愿者（0.8；0.2 - 1.3）相比，结节病患者中一般有显著更高比例的AM表达Ki - 67抗原（中位数为3.0；范围1.1 - 5.5）。在结节病中，未成熟和成熟的AM亚群均观察到增殖现象。在健康志愿者和结节病患者中，很少观察到增殖的PBM[CD14 + 单核细胞（MNC）中不到0.2%]。一小部分PBM显示出RFD9抗原的弱表达（MNC中不到1%）。有趣的是，PBM的增殖集中在这个亚群中（RFD9 + MNC的15%）。这些数据表明，即使是通常被认为是终末分化、几乎没有复制能力的成熟AM也能够增殖，而其血液循环中的前体细胞增殖比例相对非常低。此外，这些发现表明结节病中的肺组织创造了一个促进单核细胞增殖的环境。肺泡巨噬细胞（AM）最初被认为是吞噬性清除细胞（哈姆和科马克，1979年），但目前已知它们在几种肺部疾病中也启动和调节炎症和免疫过程（赫斯科维茨，1985年；乌纳纽和艾伦，1987年；西比勒和雷诺兹，1990年）。AM被认为代表单核吞噬细胞系统中更成熟的细胞，并且源自外周血单核细胞（PBM）（范·富思，1982年；金塞尔，1993年）。由于AM不断丢失（主要通过从外周气道经气管运输到咽部），局部AM群体必须不断得到补充。（摘要截断于400字）
