Regulation of steady-state neutrophil homeostasis by macrophages
Regulation of steady-state neutrophil homeostasis by macrophages
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DOI：
10.1182/blood-2010-01-265959
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发表时间：
2011-01-13
期刊：
影响因子：
20.3
通讯作者：
He, You-Wen
中科院分区：
文献类型：
--
作者：
Gordy, Claire;Pua, Heather;He, You-Wen
从炎症部位及时清除凋亡的中性粒细胞是巨噬细胞的一个重要功能;然而，巨噬细胞在稳态条件下维持中性粒细胞稳态中的作用尚不清楚。通过有条件地删除骨髓细胞中的抗凋亡基因细胞FLICE样抑制蛋白（C-FLIP），我们已经产生了一种新的小鼠模型，缺乏边缘区和骨髓基质巨噬细胞。这些小鼠出现严重的嗜中性粒细胞增多症、脾肿大、髓外造血、体重减轻以及粒细胞集落刺激因子（G-CSF）和IL-1 β（但不包括IL-17）的产生增加。c-FLIP（f/f）LysM-Cre小鼠表现出循环中性粒细胞的延迟清除，表明巨噬细胞未能有效清除凋亡中性粒细胞导致产生驱动过量粒细胞生成的细胞因子。此外，在体内阻断G-CSF而不是IL-1 R信号传导拯救了这种嗜中性粒细胞，这表明G-CSF依赖性、IL-1 β非依赖性途径在具有凋亡细胞清除缺陷的小鼠中促进中性粒细胞产生中起作用。（血。2011;117（2）：618-629）
The timely clearance of apoptotic neutrophils from inflammation sites is an important function of macrophages; however, the role of macrophages in maintaining neutrophil homeostasis under steady-state conditions is less well understood. By conditionally deleting the antiapoptotic gene cellular FLICE-like inhibitory protein (C-FLIP) in myeloid cells, we have generated a novel mouse model deficient in marginal zone and bone marrow stromal macrophages. These mice develop severe neutrophilia, splenomegaly, extramedullary hematopoiesis, decreased body weight, and increased production of granulocyte colony-stimulating factor (G-CSF) and IL-1 beta, but not IL-17. c-FLIP(f/f) LysM-Cre mice exhibit delayed clearance of circulating neutrophils, suggesting that failure of macrophages to efficiently clear apoptotic neutrophils causes production of cytokines that drive excess granulopoiesis. Further, blocking G-CSF but not IL-1R signaling in vivo rescues this neutrophilia, suggesting that a G-CSF-dependent, IL-1 beta-independent pathway plays a role in promoting neutrophil production in mice with defective clearance of apoptotic cells. (Blood. 2011;117(2):618-629)