論文 - 詳細
| RRC ID | 68630 |
|---|---|
| 著者 | Nagano F, Mizuno T, Imai M, Takahashi K, Tsuboi N, Maruyama S, Mizuno M. |
| タイトル | Expression of a Crry/p65 is reduced in acute lung injury induced by extracellular histones. |
| ジャーナル | FEBS Open Bio |
| Abstract |
Acute lung injury (ALI) occurs in patients with severe sepsis and has a mortality rate of 40-60%. Severe sepsis promotes the release of histones from dying cells, which can induce platelet aggregation, activate coagulation, and cause endothelial cell (EC) death. We previously reported that the expression of membrane complement receptor type-1-related gene Y (Crry)/p65, which plays a principal role in defence against abnormal activation of complement in the blood, is reduced in response to peritoneal mesothelial cell injury, and we hence hypothesised that a similar mechanism occurs in pulmonary ECs. In this study, we examined the role of Crry/p65 in histone-mediated ALI using an experimental animal model. In ALI model mice, exposure to extracellular histones induces lung injury and results in a decrease in Crry/p65 expression. The levels of lactic acid dehydrogenase (LDH), a marker of cell damage, were significantly increased in the serum of ALI model compared to vehicle mice. The significant inverse correlation between the expression of Crry/p65 and LDH levels in plasma revealed an association between Crry/p65 expression and cell damage. The levels of complement component 3a (C3a) were also significantly increased in the serum of the ALI model compared to vehicle mice. Notably, a C3a receptor antagonist ameliorated lung injury induced by histones. We hypothesise that extracellular histones induce complement activation via down-regulation of Crry/p65, and that C3a might serve as a therapeutic target for the treatment of ALI. |
| 巻・号 | 12(1) |
| ページ | 192-202 |
| 公開日 | 2022-1-1 |
| DOI | 10.1002/2211-5463.13322 |
| PMID | 34709768 |
| PMC | PMC8727949 |
| MeSH | Acute Lung Injury* / chemically induced Acute Lung Injury* / metabolism Animals Complement Activation Histones* / metabolism Humans Lung / metabolism Mice Receptors, Complement / metabolism Receptors, Complement 3b |
| IF | 2.231 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | UV♀2(RCB1994) |