Kupffer cell heterogeneity: functional properties of bone marrow-derived and sessile hepatic macrophages
Kupffer cell heterogeneity: functional properties of bone marrow-derived and sessile hepatic macrophages
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DOI：
10.1182/blood-2007-02-073841
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发表时间：
2007-12-01
期刊：
影响因子：
20.3
通讯作者：
Crispe, Ian Nicholas
中科院分区：
文献类型：
--
作者：
Klein, Ingo;Cornejo, Judith C.;Crispe, Ian Nicholas
Kupffer细胞在肝窦内形成一个巨大的血管内巨噬细胞床。Kupffer细胞的分化历史和多样性存在争议；一些研究认为它们来自单核细胞，而另一些研究支持它们来自肝内前体细胞的局部起源。在目前的研究中，我们使用流式细胞术和免疫组织化学方法来区分骨髓移植和原位肝移植中发现的两种Kupffer细胞亚群。其中一个亚群是辐射敏感的，并迅速从血源性前体中取代，而另一个亚群相对耐辐射且寿命较长。两者都是吞噬细胞，但只有前者被招募到炎症区域以响应CD8+T细胞的激活。我们建议将不参与免疫炎症反应的抗辐射Kupffer细胞命名为“无柄”。然而，我们没有发现证据表明这些固着库普弗细胞起源于未成熟的肝内前体细胞。我们的结论解决了一个长期存在的争议，并解释了不同的实验方法如何揭示这两个子集中的一个或两者。
Kupffer cells form a large intravascular macrophage bed in the liver sinusoids. The differentiation history and diversity of Kupffer cells is disputed; some studies argue that they are derived from blood monocytes, whereas others support a local origin from intrahepatic precursor cells. In the present study, we used both flow cytometry and immunohistochemistry to distinguish 2 subsets of Kupffer cells that were revealed in the context both of bone marrow transplantation and of orthotopic liver transplantation. One subset was radiosensitive and rapidly replaced from hematogenous precursors, whereas the other was relatively radioresistant and long-lived. Both were phagocytic but only the former population was recruited into inflammatory foci in response to CD8+ T-cell activation. We propose the name "sessile" for the radioresistant Kupffer cells that do not partici-pate in immunoinflammatory reactions. However, we found no evidence that these sessile Kupffer cells arise from immature intrahepatic precursors. Our conclusions resolve a long-standing controversy and explain how different experimental approaches may reveal one or both of these subsets.