Expression and function of c-kit in hemopoietic progenitor cells.
Expression and function of c-kit in hemopoietic progenitor cells.
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DOI：
10.1084/jem.174.1.63
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发表时间：
1991-07-01
期刊：
影响因子：
--
通讯作者：
Nishikawa S
中科院分区：
文献类型：
--
作者：
Ogawa M;Matsuzaki Y;Nishikawa S;Hayashi S;Kunisada T;Sudo T;Kina T;Nakauchi H;Nishikawa S
利用针对小鼠c-kit细胞外结构域的单克隆抗体（mab），研究了酪氨酸激酶受体c-kit在小鼠成体骨髓中的表达和功能。在成年C57BL/6小鼠中，7.8%的骨髓细胞表面表达c-kit。一半的c-kit+细胞不表达谱系标记，包括Mac-1、Gr-1、TER-119和B220，而其余的细胞共表达骨髓谱系标记，如Mac-1和Gr-1。从骨髓细胞制备中去除c-kit+细胞后，对IL-3、GM-CSF或M-CSF有反应的造血祖细胞以及在辐照受体中产生脾脏集落的造血祖细胞几乎完全消失。因此，成人骨髓中的大多数造血祖细胞表达c-kit。为了研究c-kit在成人骨髓造血中是否有任何作用，我们利用了一种抗c-kit单克隆抗体，它可以拮抗c-kit的功能。早在注射1毫克拮抗抗体ACK2 2天后，骨髓中几乎所有造血祖细胞消失，最终导致骨髓中成熟的髓系细胞和红系细胞缺失。这些结果提供了直接的证据，证明c-kit是构成性造血，特别是造血祖细胞在不同分化阶段的自我更新所必需的分子。
The expression and function of a receptor tyrosine kinase, c-kit, in the adult bone marrow of the mouse were investigated by using monoclonal antibodies (mAbs) against the extracellular domain of murine c-kit. In adult C57BL/6 mouse, 7.8% of total bone marrow cells express c-kit on their surface. Half of the c-kit+ cells do not express lineage markers including Mac-1, Gr-1, TER-119, and B220, while the remainder coexpress myeloid lineage markers such as Mac-1 and Gr-1. After c-kit+ cells were removed from the bone marrow cell preparation, hemopoietic progenitor cells reactive to IL-3, GM-CSF, or M-CSF and also those which give rise to spleen colonies in irradiated recipients disappeared almost completely. Thus, most hemopoietic progenitors in the adult bone marrow express c-kit. To investigate whether or not c-kit has any role in the hemopoiesis of adult bone marrow, we took the advantage of one of the anti-c-kit mAbs that can antagonize the function of c-kit. As early as two days after the injection of 1 milligram of an antagonistic antibody, ACK2, almost all hemopoietic progenitor cells disappeared from the bone marrow, which eventually resulted in the absence of mature myeloid and erythroid cells in the bone marrow. These results provide direct evidence that c-kit is an essential molecule for constitutive intramarrow hemopoiesis, especially for the self-renewal of hemopoietic progenitor cells at various stages of differentiation.
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64.5
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