Induction of Live Cell Phagocytosis by a Specific Combination of Inflammatory Stimuli.
Induction of Live Cell Phagocytosis by a Specific Combination of Inflammatory Stimuli.
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DOI：
10.1016/j.ebiom.2017.07.011
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发表时间：
2017-08
期刊：
影响因子：
11.1
通讯作者：
Hanayama R
中科院分区：
文献类型：
--
作者：
Ishidome T;Yoshida T;Hanayama R
严重的过度炎症状况可导致巨噬细胞的不受控制的活化，以及随后的活细胞吞噬作用。然而，炎症刺激和不受控制的巨噬细胞吞噬活细胞之间的关系知之甚少。为了鉴定这一过程的介质，我们通过用CpG DNA、干扰素-γ和抗白细胞介素-10受体抗体刺激巨噬细胞来建立活细胞的吞噬试验。在这个模型中，各种细胞表面受体上调巨噬细胞，并诱导活细胞的吞噬作用，在Rac 1依赖性的方式。随后对ICAM-1、VCAM-1和这两种受体的抑制分别在体外和体内消除了活T细胞、骨髓细胞和B细胞的吞噬作用。具体而言，在Icam-1缺陷小鼠中，由于巨噬细胞的体内活化而导致的淋巴细胞数量的减少得到改善。此外，ICAM-1或VCAM-1在非吞噬NIH 3 T3细胞中的过表达导致活细胞的主动吞噬。这些数据表明的分子机制，潜在的活细胞吞噬引起的过度炎症，这个实验模型将是有用的，以澄清噬血细胞的病理生理机制，并指出治疗目标。炎症刺激的特定组合诱导活细胞的吞噬作用在巨噬细胞上诱导的ICAM-1和VCAM-1介导活细胞吞噬作用在Icam-1缺陷小鼠中改善了噬血作用在严重的炎症条件下，巨噬细胞被过度活化并开始吞噬活血细胞及其前体，这一过程称为“噬血作用”。噬血细胞作用伴随炎症性疾病，如感染、恶性肿瘤或自身免疫性疾病，但引起噬血细胞作用的分子机制仍不清楚。我们建立了噬血细胞作用的体外细胞培养模型，发现ICAM-1和VCAM-1在巨噬细胞上被特定的炎性刺激物组合诱导介导噬血细胞作用。我们希望我们的研究结果将促进噬血细胞综合征的治疗方法的发展。
Conditions of severe hyper-inflammation can lead to uncontrolled activation of macrophages, and the ensuing phagocytosis of live cells. However, relationships between inflammatory stimuli and uncontrolled phagocytosis of live cells by macrophages are poorly understood. To identify mediators of this process, we established phagocytosis assays of live cells by stimulating macrophages with CpG DNA, interferon-γ, and anti-interleukin-10 receptor antibody. In this model, various cell surface receptors were upregulated on macrophages, and phagocytosis of live cells was induced in a Rac1-dependent manner. Subsequent inhibition of the ICAM-1, VCAM-1, and both of these receptors abolished in vitro and in vivo phagocytosis of live T cells, myeloid cells, and B cells, respectively. Specifically, the reduction in lymphocyte numbers due to in vivo activation of macrophages was ameliorated in Icam-1-deficient mice. In addition, overexpression of ICAM-1 or VCAM-1 in non-phagocytic NIH3T3 cells led to active phagocytosis of live cells. These data indicate molecular mechanisms underlying live cell phagocytosis induced by hyper-inflammation, and this experimental model will be useful to clarify the pathophysiological mechanisms of hemophagocytosis and to indicate therapeutic targets. A specific combination of inflammatory stimuli induce phagocytosis of live cells ICAM-1 and VCAM-1 induced on macrophages mediate live cell phagocytosis Hemophagocytosis was ameliorated in Icam-1-deficient mice Under severe inflammatory conditions, macrophages are hyper-activated and start to eat live blood cells and their precursors, a process known as “hemophagocytosis”. Hemophagocytosis accompanies with inflammatory diseases such as infections, malignancies, or autoimmune diseases, but molecular mechanisms that cause hemophagocytosis remain unclear. We established in vitro cell culture model of hemophagocytosis and found that ICAM-1 and VCAM-1 were induced on macrophages by a specific combination of inflammatory stimuli to mediate hemophagocytosis. We expect that our findings will facilitate the development of therapeutic approaches against the hemophagocytic syndromes.
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DOI：
10.1073/pnas.0803677105
发表时间：
2008-07-08
影响因子：
11.1
作者：
Nakaya, Michio;Kitano, Masahiro;Nagata, Shigekazu
通讯作者：
Nagata, Shigekazu
影响因子：
2.2
作者：
Miksa, Michael;Kornura, Hidefumi;Wu, Rongqian;Shah, Kavin G.;Wang, Ping
通讯作者：
Wang, Ping
白细胞跨内皮迁移的机制。
DOI：
10.1146/annurev-pathol-011110-130224
发表时间：
2011
期刊：
Annual review of pathology
影响因子：
--
作者：
Muller WA
通讯作者：
Muller WA
DOI：
10.1038/nrrheum.2015.179
发表时间：
2016-05
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Grom AA;Horne A;De Benedetti F
通讯作者：
De Benedetti F
影响因子：
3.8
作者：
Frausto-Del-Rio, Dulce;Soto-Cruz, Isabel;Ortega, Enrique
通讯作者：
Ortega, Enrique