HMGB1 and cord blood: its role as immuno-adjuvant factor in innate immunity.
HMGB1 and cord blood: its role as immuno-adjuvant factor in innate immunity.
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HMGB1和脐带血：其在先天免疫中作为免疫辅助因素的作用。
DOI：
10.1371/journal.pone.0023766
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Mancino G
中科院分区：
文献类型：
--
作者：
Ciucci A;Gabriele I;Percario ZA;Affabris E;Colizzi V;Mancino G
在新生儿中，先天免疫系统在原发性感染期间在产生最初不完全有效的适当适应性免疫应答之前提供必要的保护。先天免疫应答由来源于微生物的分子或宿主细胞的损伤/死亡引起并持续。这些被统称为损伤相关分子模式（DAMP）分子。高迁移率族蛋白B1（HMGB 1），以前被认为是唯一的核因子，最近已被确定为DAMP分子。当它被炎症细胞主动分泌或从坏死细胞被动释放时，HMGB 1介导对感染、损伤和炎症的反应，诱导树突状细胞成熟和T辅助细胞-1-细胞反应。为了表征HMGB 1在新生儿先天性和不成熟防御机制中的作用，与成人外周血（PB）单核细胞相比，分析了人脐带血（CB）单核细胞的HMGB 1表达。通过流式细胞术和western blot分析，我们观察到在CB和PB细胞中：i）HMGB 1主要表达在髓样树突状细胞前体细胞和淋巴细胞的细胞表面膜上ii）模拟感染的不同促炎刺激物或分子增加HMGB 1的细胞表面表达以及其分泌到细胞外环境中; iii）用合成分子如氨基二膦酸盐（AB）（鉴定为γδ T细胞抗原）处理，触发单核细胞以及γδ T淋巴细胞上HMGB 1表达的上调，诱导其分泌。其分泌的调节和HMGB 1介导的单核细胞迁移表明HMGB 1通过γδ T淋巴细胞和髓样树突状细胞前体（先天免疫的基本组分）的参与，在不成熟系统（如CB）中作为免疫应答的调节剂。此外，先前以其免疫调节和免疫佐剂能力为特征的AB触发的HMGB 1表达/分泌增加表明免疫调节可能代表新生儿和成人病理学的新治疗方法。
In newborn the innate immune system provides essential protection during primary infections before the generation of an appropriate adaptive immune response that is initially not fully operative. Innate immune response is evoked and perpetuated by molecules derived from microorganisms or by the damage/death of host cells. These are collectively known as damage-associated molecular-pattern (DAMP) molecules. High-mobility group box 1 protein (HMGB1) or amphoterin, which previously was considered to be only a nuclear factor, has been recently identified as a DAMP molecule. When it is actively secreted by inflammatory cells or passively released from necrotic cells, HMGB1 mediates the response to infection, injury and inflammation, inducing dendritic cells maturation and T helper-1-cell responses. To characterize the role of HMGB1 in the innate and immature defense mechanisms in newborns, human cord blood (CB) mononuclear cells, in comparison to adult peripheral blood (PB) mononuclear cells, have been analyzed for its expression. By flow cytometry and western blot analysis, we observed that in CB and PB cells: i) HMGB1 is expressed on cell surface membranes of myeloid dendritic cell precursors, mostly, and lymphocytes (gamma/delta and CD4+ T cells) to a lesser extent; ii) different pro-inflammatory stimuli or molecules that mimic infection increased cell surface expression of HMGB1 as well as its secretion into extracellular environment; iii) the treatment with synthetic molecules such as aminobisphosphonates (ABs), identified to be γδ T cell antigens, triggered up-regulation of HMGB1 expression on mononuclear cells, as well γδ T lymphocytes, inducing its secretion. The modulation of its secretion and the HMGB1-mediated migration of monocytes indicated HMGB1 as regulator of immune response in an immature system, like CB, through engagement of γδ T lymphocytes and myeloid dendritic cell precursors, essential components of innate immunity. In addition, the increased HMGB1 expression/secretion triggered by ABs, previously characterized for their immuno-modulating and immune-adjuvant capabilities, indicated that immunomodulation might represent a new therapeutical approach for neonatal and adult pathologies.
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