Mannan-binding lectin regulates dendritic cell maturation and cytokine production induced by lipopolysaccharide.

Mannan-binding lectin regulates dendritic cell maturation and cytokine production induced by lipopolysaccharide.
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甘露聚糖结合凝集素调节脂多糖诱导的树突状细胞成熟和细胞因子产生

DOI:
10.1186/1471-2172-12-1
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发表时间:
2011-01-01
期刊:
影响因子:
3
通讯作者:
Chen Z
Chen Z
中科院分区:
医学4区
文献类型:
--
作者:
Wang M;Zhang Y;Chen Y;Zhang L;Lu X;Chen Z

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背景甘露聚糖结合凝集素(Mannan-binding lectin,MBL)是存在于血清中的一种模式识别分子,通过激活补体和促进调理吞噬作用参与天然免疫防御。树突状细胞(Dendritic cells,DC)是一种专职的抗原呈递细胞(antigen presenting cells,APC),在获得性免疫的启动中起着重要作用。脂多糖(LPS)已被证明是炎症反应和免疫调节的强激活剂。结果MBL在较高浓度(10-20 μg/ml)下显著减弱LPS诱导的单核细胞来源的DC(MDCs)成熟和促炎细胞因子(例如,IL-12和TNF-α),并抑制其激活同种异体T淋巴细胞的能力。它结合到未成熟的MDCs在生理钙浓度,并在超生理钙浓度是最佳的。MBL还可直接与未成熟MDCs结合,减弱LPS与细胞表面的结合,从而降低LPS诱导的MDCs核因子-κB(NF-κB)活性。这项研究支持MBL在调节适应性免疫反应和炎症反应中的重要作用。
BackgroundMannan-binding lectin (MBL) is a pattern-recognition molecule present in serum, which is involved in the innate immune defense by activating complement and promoting opsonophagocytosis. Dendritic cells (DCs) are professional antigen presenting cells (APCs) that are crucial for the initiation of adaptive immunity. Lipopolysaccharide (LPS) has been shown to be a strong activator of the inflammatory response and immune regulation. We first examined whether MBL modulated LPS-induced cellular responses, then investigated possible mechanisms of its inhibitory effect.ResultsMBL at higher concentrations (10-20 μg/ml) significantly attenuated LPS-induced maturation of monocyte-derived DCs (MDCs) and production of proinflammatory cytokines (e.g., IL-12 and TNF-α), and inhibited their ability to activate allogeneic T lymphocytes. It bound to immature MDCs at physiological calcium concentrations, and was optimal at supraphysiological calcium concentrations. MBL also bound directly to immature MDCs and attenuated the binding of LPS to the cell surfaces, resulting in decreased LPS-induced nuclear factor-κB (NF-κB) activity in these cells.ConclusionAll these data suggest that MBL could affect the functions of DCs by modifying LPS-induced cellular responses. This study supports an important role for MBL in the regulation of adaptive immune responses and inflammatory responses.
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