FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis
FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis
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DOI：
10.1182/blood-2009-11-252841
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发表时间：
2010-12-02
期刊：
影响因子：
20.3
通讯作者：
Pope, Richard M.
中科院分区：
文献类型：
--
作者：
Huang, Qi-Quan;Perlman, Harris;Pope, Richard M.
FLIP 是一种成熟的死亡受体介导的细胞凋亡抑制剂。为了确定其在骨髓细胞中的重要体内作用，我们生成并表征了在骨髓谱系中条件性缺失 Flip 的小鼠。骨髓特异性 Flip 缺陷小鼠表现出生长迟缓、过早死亡和脾肿大，并伴有结构和髓外造血的改变。他们还表现出循环中性粒细胞和多器官中性粒细胞浸润的显着增加。相比之下，虽然循环炎症单核细胞也显着增加，但脾脏、淋巴结和腹膜腔中的巨噬细胞却减少了。在离体培养中，当Flip被删除时，骨髓祖细胞无法分化为巨噬细胞。使用来自 Flip 缺陷型小鼠和野生型小鼠的细胞进行的混合骨髓嵌合体实验并未表现出炎症表型。这些观察结果表明 FLIP 对于巨噬细胞分化和粒细胞生成的稳态调节是必需的。 （血。2010；116(23):4968-4977）
FLIP is a well-established suppressor of death receptor-mediated apoptosis. To define its essential in vivo role in myeloid cells, we generated and characterized mice with Flip conditionally deleted in the myeloid lineage. Myeloid specific Flip-deficient mice exhibited growth retardation, premature death, and splenomegaly with altered architecture and extramedullary hematopoiesis. They also displayed a dramatic increase of circulating neutrophils and multiorgan neutrophil infiltration. In contrast, although circulating inflammatory monocytes were also significantly increased, macrophages in the spleen, lymph nodes, and the peritoneal cavity were reduced. In ex vivo cultures, bone marrow progenitor cells failed to differentiate into macrophages when Flip was deleted. Mixed bone marrow chimera experiments using cells from Flip-deficient and wild-type mice did not demonstrate an inflammatory phenotype. These observations demonstrate that FLIP is necessary for macrophage differentiation and the homeostatic regulation of granulopoiesis. (Blood. 2010;116(23):4968-4977)