Galectins distinctively regulate central monocyte and macrophage function

Galectins distinctively regulate central monocyte and macrophage function
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DOI:
10.1016/j.cellimm.2011.06.003
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发表时间:
2011-01-01
影响因子:
4.3
通讯作者:
Sturm, Andreas
Sturm, Andreas
中科院分区:
医学4区
文献类型:
--
作者:
Paclik, Daniela;Werner, Lael;Sturm, Andreas

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单核细胞和巨噬细胞连接先天免疫系统和适应性免疫系统,并保护宿主免受外部世界的伤害。在炎症性疾病中,它们的激活导致组织损伤。半乳糖凝集素已成为免疫系统的中央调节剂。流式细胞仪测定Gal-1、Gal-2、Gal-3和Gal-4与单核/巨噬细胞的结合、活化、细胞因子分泌和凋亡,Transwell系统测定其迁移,吞噬试验测定其吞噬功能。在我们的研究中,Gal-1、Gal-2、Gal-4和部分Gal-3与单核细胞/巨噬细胞结合。半乳糖凝集素防止沙门氏菌诱导的MHCII上调。不同的半乳糖凝集素明显诱导细胞因子的释放。在Gal-2或Gal-4存在下共培养的巨噬细胞的上清液显著限制T细胞活化。此外,所有测试的半乳糖凝集素均显著抑制单核细胞迁移。最后,我们首次发现半乳糖凝集素诱导单核细胞凋亡,但不诱导巨噬细胞凋亡。我们的研究为半乳糖凝集素明显调节中枢单核细胞/巨噬细胞功能提供了证据。通过巨噬细胞引发抑制T细胞功能,我们表明半乳糖凝集素连接先天性和适应性免疫系统,并提供了新的见解糖结合蛋白的作用。(C)2011 Elsevier Inc. All rights reserved.
Monocytes and macrophages link the innate and adaptive immune systems and protect the host from the outside world. In inflammatory disorders their activation leads to tissue damage. Galectins have emerged as central regulators of the immune system. However, if they regulate monocyte/macrophage physiology is still unknown.Binding of Gal-1, Gal-2, Gal-3 and Gal-4 to monocytes/macrophages, activation, cytokine secretion and apoptosis were determined by FACS, migration by Transwell system and phagocytosis by phagotest. Supernatants from macrophages co-cultured with galectins revealed their influence on T-cell function.In our study Gal-1, Gal-2, Gal-4, and partly Gal-3 bound to monocytes/macrophages. Galectins prevented Salmonella-induced MHCII upregulation. Cytokine release was distinctly induced by different galectins. T-cell activation was significantly restricted by supernatants of macrophages co-cultured in the presence of Gal-2 or Gal-4. Furthermore, all galectins tested significantly inhibited monocyte migration. Finally, we showed for the first time that galectins induce potently monocyte, but not macrophage apoptosis.Our study provides evidence that galectins distinctively modulate central monocyte/macrophage function. By inhibiting T-cell function via macrophage priming, we show that galectins link the innate and adaptive immune systems and provide new insights into the action of sugar-binding proteins. (C) 2011 Elsevier Inc. All rights reserved.