Hemophagocytosis causes a consumptive anemia of inflammation.

Hemophagocytosis causes a consumptive anemia of inflammation.
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DOI:
10.1084/jem.20102538
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发表时间:
2011-06-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Jordan MB
Jordan MB
中科院分区:
其他
文献类型:
--
作者:
Zoller EE;Lykens JE;Terrell CE;Aliberti J;Filipovich AH;Henson PM;Jordan MB

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干扰素-γ通过直接作用于巨噬细胞刺激吞噬血液的巨噬细胞,促进血细胞的吞噬和摄取。严重炎症时,常可观察到病因不明的红细胞减少症。吞血反应是吞血巨噬细胞的组织学表现,可见于吞血细胞淋巴组织细胞增多症和其他炎症性疾病。虽然假设这些现象是有联系的,但促进急性炎症相关性细胞减少的机制尚不清楚。我们报道,干扰素γ(干扰素-γ)是小鼠在不同微生物感染过程中观察到的急性贫血的关键驱动因素。此外,全身暴露于生理水平的干扰素-γ足以引起急性细胞减少症和吞噬血细胞症。证明了吞噬血细胞的重要性,我们发现干扰素-γ直接作用于体内的巨噬细胞,改变内吞作用,刺激血细胞摄取,导致严重贫血。这些发现定义了一种独特的病理过程,具有广泛的临床和免疫学意义,我们称之为炎症性消耗性贫血。
IFN-γ stimulates blood-eating macrophages (hemophagocytes) by acting directly on macrophages to promote phagocytosis and uptake of blood cells. Cytopenias of uncertain etiology are commonly observed in patients during severe inflammation. Hemophagocytosis, the histological appearance of blood-eating macrophages, is seen in the disorder hemophagocytic lymphohistiocytosis and other inflammatory contexts. Although it is hypothesized that these phenomena are linked, the mechanisms facilitating acute inflammation-associated cytopenias are unknown. We report that interferon γ (IFN-γ) is a critical driver of the acute anemia observed during diverse microbial infections in mice. Furthermore, systemic exposure to physiologically relevant levels of IFN-γ is sufficient to cause acute cytopenias and hemophagocytosis. Demonstrating the significance of hemophagocytosis, we found that IFN-γ acts directly on macrophages in vivo to alter endocytosis and provoke blood cell uptake, leading to severe anemia. These findings define a unique pathological process of broad clinical and immunological significance, which we term the consumptive anemia of inflammation.
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