The NLRP3 inflammasome in macrophages is stimulated by cell-free hemoglobin.
The NLRP3 inflammasome in macrophages is stimulated by cell-free hemoglobin.
复制标题
巨噬细胞中的NLRP3炎症体是由无细胞血红蛋白刺激的。
DOI：
10.14814/phy2.14589
复制
发表时间：
2020-11
影响因子：
2.5
通讯作者：
Bastarache JA
中科院分区：
文献类型：
--
作者：
Shaver CM;Landstreet SR;Pugazenthi S;Scott F;Putz N;Ware LB;Bastarache JA
Cell‐free hemoglobin (CFH) is associated with severe lung injury in human patients and is sufficient to induce airspace inflammation and alveolar–capillary barrier dysfunction in an experimental model of acute lung injury. The mechanisms through which this occurs are unknown. One key pathway which regulates inflammation during acute lung injury is the NLRP3 inflammasome. Because CFH can act as a damage‐associated molecular pattern, we hypothesized that CFH may activate the NLRP3 inflammasome during acute lung injury. Primary mouse alveolar macrophages and cultured murine macrophages exposed to CFH (0–1 mg/ml) for 24 hr demonstrated robust upregulation of the NLRP3 inflammasome components NLRP3, caspase‐1, and caspase‐11. Maximal induction of the NLRP3 inflammasome by CFH required TLR4. Compared to wild‐type controls, mice lacking NLRP3 developed less airspace inflammation (2.7 × 105 cells/ml in bronchoalveolar lavage fluid versus. 1.1 × 105/ml, p = .006) after exposure to intratracheal CFH. Together, these data demonstrate that CFH can stimulate the NLRP3 inflammasome in macrophages and that this pathway may be important in the pathogenesis of CFH‐induced acute lung injury. Cell‐free hemoglobin is associated with severe lung injury in human patients and is sufficient to induce airspace inflammation and alveolar–capillary barrier dysfunction in an experimental model of acute lung injury. Here, we investigate the role of the NLRP3 inflammasome in lung injury caused by cell‐free hemoglobin using in vitro and in vivo model systems. Our results show that cell‐free hemoglobin increases NLRP3 expression in alveolar macrophages and that mice lacking NLRP3 have reduced inflammation in response to cell‐free hemoglobin, suggesting that NLRP3 has an important role in acute lung injury caused by cell‐free hemoglobin.
登录
查看更多内容
高铁蛋白是一种内源性Toll样受体4配体与亚蛛网膜下腔出血。
影响因子：
5.6
作者：
Kwon MS;Woo SK;Kurland DB;Yoon SH;Palmer AF;Banerjee U;Iqbal S;Ivanova S;Gerzanich V;Simard JM
通讯作者：
Simard JM
ROS 介导的 NLRP3 炎症小体活性对于烧伤引起的急性肺损伤至关重要。
影响因子：
4.6
作者：
Han S;Cai W;Yang X;Jia Y;Zheng Z;Wang H;Li J;Li Y;Gao J;Fan L;Hu D
通讯作者：
Hu D
影响因子：
10.6
作者：
Ma L;Shaver CM;Grove BS;Mitchell DB;Wickersham NE;Carnahan RH;Cooper TL;Brake BE;Ware LB;Bastarache JA
通讯作者：
Bastarache JA
影响因子：
5.5
作者：
Fukumoto, Jutaro;Fukumoto, Itsuko;Kolliputi, Narasaiah
通讯作者：
Kolliputi, Narasaiah
影响因子：
32.4
作者：
Gaidt, Moritz M.;Ebert, Thomas S.;Hornung, Veit
通讯作者：
Hornung, Veit