Evaluation of the contribution of multiple DAMPs and DAMP receptors in cell death-induced sterile inflammatory responses.
Evaluation of the contribution of multiple DAMPs and DAMP receptors in cell death-induced sterile inflammatory responses.
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DOI：
10.1371/journal.pone.0104741
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rock KL
中科院分区：
文献类型：
--
作者：
Kataoka H;Kono H;Patel Z;Kimura Y;Rock KL
当细胞在体内因坏死而死亡时，它们刺激炎症反应。据认为，当受损细胞暴露促炎分子时，这种反应被触发，这些促炎分子统称为损伤相关分子模式（DAMP），其被先天性或适应性免疫系统的细胞或可溶性分子识别。已经鉴定了几种假定的DAMP和/或其受体，但它们是否以及在多大程度上参与体内反应尚不完全清楚，并且它们以前没有在相同的模型中进行过并排比较。这项研究的重点是评估已经提出或可能参与细胞死亡诱导的炎症的多种机制的贡献：补体的第三组分（C3），ATP（及其受体P2 X7），抗体，C型凝集素受体Mincle（Clec 4 e）和蛋白酶激活受体2（PAR 2）。我们研究了这些因子在细胞死亡诱导的腹膜死亡细胞炎症和对乙酰氨基酚诱导的肝损伤中的作用。我们发现缺乏抗体、C3或PAR 2的小鼠对垂死细胞的炎症反应受损。相比之下，在遗传上缺乏Mincle、P2 X7受体或用腺苷三磷酸双磷酸酶处理以耗尽ATP的小鼠的腹膜或肝脏中，炎症细胞死亡没有减少。这些结果表明，抗体、补体和PAR 2有助于细胞死亡诱导的炎症，但在至少2种不同的体内模型中，Mincle和ATP-P2 X7受体不是该应答所必需的。
When cells die by necrosis in vivo they stimulate an inflammatory response. It is thought that this response is triggered when the injured cells expose proinflammatory molecules, collectively referred to as damage associated molecular patterns (DAMPs), which are recognized by cells or soluble molecules of the innate or adaptive immune system. Several putative DAMPs and/or their receptors have been identified, but whether and how much they participate in responses in vivo is incompletely understood, and they have not previously been compared side-by-side in the same models. This study focuses on evaluating the contribution of multiple mechanisms that have been proposed to or potentially could participate in cell death-induced inflammation: The third component of complement (C3), ATP (and its receptor P2X7), antibodies, the C-type lectin receptor Mincle (Clec4e), and protease-activated receptor 2 (PAR2). We investigate the role of these factors in cell death-induced inflammation to dead cells in the peritoneum and acetaminophen-induced liver damage. We find that mice deficient in antibody, C3 or PAR2 have impaired inflammatory responses to dying cells. In contrast there was no reduction in inflammation to cell death in the peritoneum or liver of mice that genetically lack Mincle, the P2X7 receptor or that were treated with apyrase to deplete ATP. These results indicate that antibody, complement and PAR2 contribute to cell death-induced inflammation but that Mincle and ATP- P2X7 receptor are not required for this response in at least 2 different in vivo models.
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DOI：
10.1084/jem.133.4.885
发表时间：
1971-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hill JH;Ward PA
通讯作者：
Ward PA
影响因子：
82.9
作者：
Chen, Chun-Jen;Kono, Hajime;Rock, Kenneth L.
通讯作者：
Rock, Kenneth L.
影响因子：
2.7
作者：
KAMIIKE, W;WATANABE, F;KAWASHIMA, Y
通讯作者：
KAWASHIMA, Y
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
82.9
作者：
Huber-Lang, Markus;Sarma, J. Vidya;Ward, Peter A.
通讯作者：
Ward, Peter A.