Cutting Edge: A Critical Role of Nitrogen Oxide in Preventing Inflammation upon Apoptotic Cell Clearance1

Cutting Edge: A Critical Role of Nitrogen Oxide in Preventing Inflammation upon Apoptotic Cell Clearance1
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最前沿:一氧化氮在预防凋亡细胞清除时发生炎症方面的关键作用1

DOI:
10.4049/jimmunol.179.6.3407
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发表时间:
2007
期刊:
The Journal of Immunology
影响因子:
--
通讯作者:
Yoshiro Kobayashi
Yoshiro Kobayashi
中科院分区:
--
文献类型:
--
作者:
T. Shibata;K. Nagata;Yoshiro Kobayashi

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凋亡细胞被吞噬细胞清除,而不会引起炎症。在体内,抗炎介质是否能阻止中性粒细胞在凋亡细胞清除过程中的渗透在很大程度上仍未得到解决。在本研究中,我们发现,在X射线诱导胸腺细胞凋亡后,诱导型一氧化氮合酶基因敲除(KO)小鼠比野生型(WT)小鼠表现出更高水平的中性粒细胞浸润以及胸腺中MIP-2和角质形成细胞衍生趋化因子(KC)的产生。此外,给予受X射线照射的WT小鼠给予一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯,可通过增加MIP-2和KC的产生,增加中性粒细胞的渗透水平,从而达到KO小鼠的水平。此外,经x射线照射的KO鼠胸腺巨噬细胞比WT鼠的胸腺巨噬细胞产生更多的MIP-2和KC。因此,尽管细胞凋亡被认为是非炎症性的,但这实际上是通过产生免疫抑制信号来实现的,这些信号可以对抗促炎症趋化因子如MIP-2和KC。
Apoptotic cells are removed by phagocytes without causing inflammation. It remains largely unresolved whether anti-inflammatory mediators prevent neutrophil infiltration upon apoptotic cell clearance in vivo. In this study, we showed that, upon induction of apoptosis in the thymus by x-ray, inducible NO synthase knockout (KO) mice exhibited higher levels of neutrophil infiltration and production of MIP-2 and keratinocyte-derived chemokine (KC) in the thymus than wild-type (WT) mice. Furthermore, administration of NG-nitro-l-arginine methyl ester, an inhibitor of NO synthase, to x-irradiated WT mice increased the level of neutrophil infiltration to that of KO mice by the augmentation of MIP-2 and KC production. Additionally, thymic macrophages isolated from x-irradiated KO mice produced more MIP-2 and KC than those from WT mice. Thus, although apoptosis is believed to be noninflammatory, this is actually achieved by the production of immunosuppressive signals such as NO that counteract proinflammatory chemokines such as MIP-2 and KC.
DOI: 10.1172/jci1112
发表时间: 1998-02-15
影响因子: 15.9
作者:
Fadok, VA;Bratton, DL;Henson, PM
通讯作者: Henson, PM
DOI: 10.1073/pnas.88.11.4651
发表时间: 1991-06-01
影响因子: 11.1
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发表时间: 2002-01-01
影响因子: 15.9
作者:
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通讯作者: Henson, PM