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外周血单个核细胞在热损伤反应中表现出分解代谢亢进活性,这与主要组织相容性复合体I类分子(MHC I)表达减少相关。

Peripheral blood mononuclear cells exhibit hypercatabolic activity in response to thermal injury correlating with diminished MHC I expression.

作者信息

Madihally S V, Toner M, Yarmush M L, Mitchell R N

机构信息

Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, Massachusetts, USA.

出版信息

J Trauma. 2001 Mar;50(3):500-9. doi: 10.1097/00005373-200103000-00015.

Abstract

BACKGROUND

Muscle wasting is one of the major consequences of severe injury or infection. Although the mechanisms underlying this hypercatabolic state are not completely characterized, it was hypothesized that other cells in the body would be similarly affected. In particular, we sought to determine whether lymphoid cell populations experienced increased protein turnover after burn injury in a fashion analogous to that seen in skeletal muscle.

METHODS

BALB/c mice received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 after treatment, skeletal muscle, peripheral blood, spleen, and lymph nodes were harvested from both groups. Protein synthesis and degradation rates were measured using 14C-phenylalanine incorporation and tyrosine release. Lymphocyte subpopulations (CD4 and CD8 T cells, macrophages, and B cells) and expression of major histocompatibility complex I (MHC I) molecules were assessed by flow cytometry.

RESULTS

The burn model used in this study resulted in increased skeletal muscle protein turnover in the first 2 days after injury. Protein synthetic and degradation rates of peripheral blood mononuclear cells (PBMNCs) in burned mice also demonstrated comparable changes, but persisted through day 7. Splenocytes showed similar hypercatabolic effects, whereas lymph node cells showed no change. Cell viability analysis confirmed that the observed alterations were not caused by cell death. MHC I expression was depressed in tandem with the increased catabolic rate in PBMNCs.

CONCLUSION

This study demonstrates that various lymphoid populations undergo protein catabolic changes similar to those characteristically observed in skeletal muscle, and these correlated with diminished MHC I expression. Moreover, PBMNCs exhibited prolonged sensitivity to burn injury, of a duration exceeding that observed in skeletal muscles or other lymphoid tissues.

摘要

背景

肌肉消耗是严重损伤或感染的主要后果之一。尽管这种分解代谢亢进状态的潜在机制尚未完全明确,但据推测,体内其他细胞也会受到类似影响。特别是,我们试图确定烧伤后淋巴细胞群体的蛋白质周转率是否会以类似于骨骼肌的方式增加。

方法

BALB/c小鼠接受20%体表面积烧伤或对照假手术治疗。治疗后第1、2和7天,从两组小鼠中采集骨骼肌、外周血、脾脏和淋巴结。使用14C-苯丙氨酸掺入和酪氨酸释放来测量蛋白质合成和降解率。通过流式细胞术评估淋巴细胞亚群(CD4和CD8 T细胞、巨噬细胞和B细胞)以及主要组织相容性复合体I(MHC I)分子的表达。

结果

本研究中使用的烧伤模型导致损伤后前两天骨骼肌蛋白质周转率增加。烧伤小鼠外周血单个核细胞(PBMNCs)的蛋白质合成和降解率也显示出类似变化,但持续到第7天。脾细胞表现出类似的分解代谢亢进作用,而淋巴结细胞则无变化。细胞活力分析证实,观察到的改变不是由细胞死亡引起的。PBMNCs中MHC I表达与分解代谢率增加同步降低。

结论

本研究表明,各种淋巴细胞群体经历了与骨骼肌中典型观察到的类似的蛋白质分解代谢变化,并且这些变化与MHC I表达降低相关。此外,PBMNCs对烧伤损伤表现出延长的敏感性,其持续时间超过在骨骼肌或其他淋巴组织中观察到的时间。

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