Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells

Antigen presentation by macrophages is enhanced by the uptake of necrotic, but not apoptotic, cells
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DOI:
10.1046/j.1365-2249.2002.01774.x
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发表时间:
2002-02-01
影响因子:
4.6
通讯作者:
Rees, AJ
Rees, AJ
中科院分区:
医学3区
文献类型:
--
作者:
Barker, RN;Erwig, LP;Rees, AJ

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本研究的目的是确定坏死或凋亡细胞的吞噬作用是否会影响小鼠骨髓源性巨噬细胞的抗原呈递。在摄取坏死的中性粒细胞后,巨噬细胞能够在体外刺激针对回忆抗原白蛋白和促分裂原伴刀豆球蛋白A的显著更高的T细胞增殖。吞噬凋亡的中性粒细胞后没有观察到这种作用。流式细胞术显示,在4小时的摄入,已采取了坏死细胞的巨噬细胞比那些吞噬凋亡细胞表达更高水平的CD40。与未处理的对照组相比,用凋亡但不坏死的中性粒细胞脉冲的巨噬细胞培养物含有较高水平的转化生长因子β 1,但较低浓度的肿瘤坏死因子α。我们对这些结果的解释是,由于CD40的快速上调,已经摄取坏死中性粒细胞的巨噬细胞以更高的效率共刺激T细胞,而那些已经摄取凋亡细胞的巨噬细胞不仅在共刺激中无效,而且还分泌抑制性细胞因子。
The aim of this study was to determine whether phagocytosis of necrotic or apoptotic cells affects antigen presentation by murine bone marrow-derived macrophages. After uptake of necrotic neutrophils, macrophages were able to stimulate significantly higher T cell proliferation in vitro against both the recall antigen albumin and the mitogen concanavalin A. No such effect was seen following phagocytosis of apoptotic neutrophils. Flow cytometry revealed that, within 4h of ingestion, macrophages that had taken up the necrotic cells expressed higher levels of CD40 than those that had phagocytosed apoptotic cells. Macrophage cultures pulsed with apoptotic, but not necrotic, neutrophils contained higher levels of transforming growth factor beta1, but lower concentrations of tumour necrosis factor alpha, compared to untreated controls. Our interpretation of these results is that macrophages that have taken up necrotic neutrophils co-stimulate T cells with greater efficiency due to rapid CD40 up-regulation, whereas those that have ingested apoptotic cells are not only ineffective in co-stimulation, but also secrete inhibitory cytokine.