Deficiency of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality and Lung Injury in Mice.
Deficiency of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality and Lung Injury in Mice.
复制标题
急性时相血清淀粉样蛋白A缺乏可加重脓毒症小鼠的死亡率和肺损伤。
DOI：
10.3390/ijms242417501
复制
发表时间：
2023-12-15
影响因子：
5.6
通讯作者：
Shridas, Preetha
中科院分区：
文献类型：
--
作者：
Ji, Ailing;Trumbauer, Andrea C.;Noffsinger, Victoria P.;Meredith, Luke W.;Dong, Brittany;Wang, Qian;Guo, Ling;Li, Xiangan;De Beer, Frederick C.;Webb, Nancy R.;Tannock, Lisa R.;Starr, Marlene E.;Waters, Christopher M.;Shridas, Preetha
血清淀粉样蛋白A（SAA）是一个蛋白质家族，在急性炎症状态下其血浆水平可能会增加1000倍以上。我们利用缺乏所有三种急性期SAA异构体的小鼠（SAA - TKO）研究了SAA在脓毒症中的作用。在三种实验性脓毒症小鼠模型中：盲肠结扎穿孔（CLP）、盲肠浆液（CS）注射和脂多糖（LPS）处理，SAA缺乏显著增加了死亡率。与野生型（WT）小鼠相比，CLP后SAA - TKO小鼠的肺部病理损伤加剧。在CLP 24小时后对切除的肺组织进行的大量RNA测序表明，与WT小鼠相比，SAA - TKO小鼠中与趋化因子产生、趋化因子和细胞因子介导的信号传导、中性粒细胞趋化以及中性粒细胞迁移相关的基因表达显著富集。一致地，与WT小鼠相比，脓毒症SAA - TKO小鼠肺部的髓过氧化物酶活性和中性粒细胞计数显著增加。用SAA或与高密度脂蛋白结合的SAA（SAA - HDL）对HL - 60（类中性粒细胞）细胞进行体外处理，与未处理的细胞相比，显著降低了细胞通过层粘连蛋白包被的膜的迁移。因此，SAA可能阻止中性粒细胞迁移到受损的肺部，从而减少加剧的组织损伤和死亡率。总之，我们首次证明内源性SAA在脓毒症中起保护作用，包括减轻肺损伤。
Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury.
登录
查看更多内容
脓毒症期间的中性粒细胞失调：概述和更新
影响因子：
5.3
作者：
Shen XF;Cao K;Jiang JP;Guan WX;Du JF
通讯作者：
Du JF
影响因子：
4.4
作者：
Lee, Ha Young;Kim, Sang Doo;Bae, Yoe-Sik
通讯作者：
Bae, Yoe-Sik
影响因子：
64.5
作者：
Lee, June-Yong;Hall, Jason A.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
4.4
作者：
Bannenberg, GL;Chiang, N;Serhan, CN
通讯作者：
Serhan, CN
DOI：
10.1073/pnas.74.9.4025
发表时间：
1977-01-01
影响因子：
11.1
作者：
BENDITT, EP;ERIKSEN, N
通讯作者：
ERIKSEN, N