Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation.
Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation.
复制标题
op/op 小鼠先天性石骨症的血液学特征。巨噬细胞分化异常的可能机制。
DOI：
10.1084/jem.156.5.1516
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发表时间：
1982-11-01
影响因子：
15.3
通讯作者：
Skelly, R R
中科院分区：
文献类型：
--
作者：
Wiktor-Jedrzejczak, W W;Ahmed, A;Szczylik, C;Skelly, R R
与正常同窝小鼠相比，op/op小鼠腹腔中的巨噬细胞非常少，外周血中的单核细胞数量严重减少。此外，骨硬化动物表现出造血组织分布的改变，骨髓细胞数量减少10倍。肝造血持续4周龄小鼠证明造血干细胞（HSC）的存在。此外，骨髓中HSC浓度降低，脾脏中HSC浓度升高。尽管体内单核-巨噬细胞谱系细胞缺乏，但在外源性集落刺激活性（CSA）存在下，来自op/op小鼠造血组织的祖细胞在体外形成了数量增加的单核-巨噬细胞集落。这一关键CSA的来源是由正常骨髓细胞在体外形成的基质成纤维细胞样集落条件培养基。因此，这些数据表明，op/op小鼠具有正常的单核细胞-巨噬细胞-破骨细胞祖细胞，但这些细胞不能在op/op小鼠微环境中完全分化。为了支持这一点，在来自op/op骨髓或脾脏的基质成纤维细胞样集落的培养物中，通常非常密集的巨噬细胞的伴随生长急剧减少。此外，op/op脾细胞移植到致死性照射的同窝受者导致其造血重建没有巨噬细胞缺陷的迹象。因此，op/op脾细胞不会转移疾病，并且能够在正常的体内环境中正常分化。这些观察结果支持这样的假设，即op/op小鼠中的缺陷是造血基质成纤维细胞样细胞未能释放足够量的CSA的结果，CSA是单核细胞-巨噬细胞谱系细胞正常分化所必需的。
Compared with normal littermates, the op/op mice had very few macrophages in the peritoneal cavity and severely reduced numbers of monocytes in the peripheral blood. Moreover, osteopetrotic animals demonstrated an altered distribution of hemopoietic tissue with a 10- fold decrease in the number of marrow cells. Liver hemopoiesis persisted in 4-wk-old mice as evidenced by the presence of hemopoietic stem cells (HSC). Moreover, the concentration of HSC was decreased in marrow and increased in the spleen of op/op mice. In spite of the paucity of cells of monocyte-macrophage lineage in vivo, progenitor cells from hemopoietic tissues of op/op mice formed increased numbers of monocyte-macrophage colonies in vitro in the presence of exogenous colony-stimulating activity (CSA). The source of this critical CSA was a medium conditioned by stromal fibroblastoid colonies formed in vitro by normal marrow cells. Therefore, these data suggest that op/op mice possess normal monocyte-macrophage-osteoclast progenitor cells but these cells are unable to fully differentiate in the op/op mouse microenvironment. In support of this, in cultures of stromal fibroblastoid colonies from op/op marrow or spleen, the concomitant growth of macrophages, normally very dense, was drastically reduced. Moreover, transplantation of op/op spleen cells into lethally irradiated littermate recipients resulted in their hemopoietic reconstitution without signs of macrophage defect. Thus, the op/op splenic cells do not transfer the disease and are capable of normal differentiation in normal in vivo environment. These observations support the hypothesis that the defect in op/op mice is a result of the failure of hemopoietic stromal fibroblastoid cells to release sufficient amounts of CSA necessary for normal differentiation of cells of the monocyte-macrophage lineage.