Annexin A1 regulates neutrophil clearance by macrophages in the mouse bone marrow.

Annexin A1 regulates neutrophil clearance by macrophages in the mouse bone marrow.
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膜联蛋白A1调节小鼠骨髓中巨噬细胞的中性粒细胞清除。

DOI:
10.1096/fj.11-182089
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发表时间:
2012-01
期刊:
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子:
--
通讯作者:
Rankin SM
Rankin SM
中科院分区:
其他
文献类型:
--
作者:
Dalli J;Jones CP;Cavalcanti DM;Farsky SH;Perretti M;Rankin SM

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在稳态条件下,一部分衰老的CXCR4hi中性粒细胞从循环中回到骨髓,在那里它们被骨髓巨噬细胞吞噬。在这项研究中,我们发现了抗炎分子膜联蛋白A1 (AnxA1)作为这一过程的关键调节因子的意想不到的作用。我们首先观察到,在正常水平的GM和G集落形成单位、单核细胞和巨噬细胞的同时,AnxA1 - / -小鼠骨髓中的中性粒细胞数量显著增加。虽然AnxA1 - / -小鼠骨髓中有更多的中性粒细胞,但这些细胞中更大比例是衰老的,这是由它们更高水平的CXCR4表达和膜联蛋白V结合决定的。因此,来自AnxA1 - / -小鼠的骨髓中性粒细胞在体外表现出降低的迁移能力。体外研究也表明,骨髓巨噬细胞吞噬凋亡的中性粒细胞需要AnxA1的表达,而腹膜巨噬细胞则不需要。此外,体内实验表明,在清除野生型中性粒细胞在AnxA1 - / -小鼠骨髓中的缺陷。因此,我们得出结论,巨噬细胞中AnxA1的表达是骨髓中中性粒细胞清除的关键决定因素。- Dalli, J., Jones, C. P., Cavalcanti, D. M., Farsky, S. H., Perretti, M., Rankin, S. M.:膜联蛋白A1调节小鼠骨髓中巨噬细胞对中性粒细胞的清除。
Under homeostatic conditions, a proportion of senescent CXCR4hi neutrophils home from the circulation back to the bone marrow, where they are phagocytosed by bone marrow macrophages. In this study, we have identified an unexpected role for the anti-inflammatory molecule annexin A1 (AnxA1) as a critical regulator of this process. We first observed that AnxA1−/− mice have significantly increased neutrophil numbers in their bone marrow while having normal levels of GM and G colony-forming units, monocytes, and macrophages. Although AnxA1−/− mice have more neutrophils in the bone marrow, a greater proportion of these cells are senescent, as determined by their higher levels of CXCR4 expression and annexin V binding. Consequently, bone marrow neutrophils from AnxA1−/− mice exhibit a reduced migratory capacity in vitro. Studies conducted in vitro also show that expression of AnxA1 is required for bone marrow macrophages, but not peritoneal macrophages, to phagocytose apoptotic neutrophils. Moreover, in vivo experiments indicate a defect in clearance of wild-type neutrophils in the bone marrow of AnxA1−/− mice. Thus, we conclude that expression of AnxA1 by resident macrophages is a critical determinant for neutrophil clearance in the bone marrow.— Dalli, J., Jones, C. P., Cavalcanti, D. M., Farsky, S. H., Perretti, M., Rankin, S. M. Annexin A1 regulates neutrophil clearance by macrophages in the mouse bone marrow.
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