Arshid Samina, Tahir Muhammad, Fontes Belchor, de Souza Montero Edna Frasson, Castro Mariana S, Sidoli Simone, Roepstorff Peter, Fontes Wagner
Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biology, University of Brasilia, Brasília, Brazil.
Laboratory of Surgical Physiopathology (LIM-62), Faculty of Medicine, University of São Paulo, Brazil.
Proteomics Clin Appl. 2017 Jan;11(1-2). doi: 10.1002/prca.201600001. Epub 2016 Nov 9.
In clinical conditions trauma is associated with high mortality and morbidity. Neutrophils play a key role in the development of multiple organ failure after trauma EXPERIMENTAL DESIGN: To have a detailed understanding of the neutrophil activation at primary stages after trauma, neutrophils are isolated from control and surgical trauma rats in this study. Extracted proteins are analyzed using nano liquid chromatography coupled with tandem mass spectrometry.
A total of 2924 rat neutrophil proteins are identified in our analysis, of which 393 are found differentially regulated between control and trauma groups. By using functional pathways analysis of the 190 proteins up-regulated in surgical trauma, we found proteins related to transcription initiation and protein biosynthesis. On the other hand, among the 203 proteins down-regulated in surgical trauma we found enrichment for proteins of the immune response, proteasome degradation and actin cytoskeleton. Overall, enzyme prediction analysis revealed that regulated enzymes are directly involved in neutrophil apoptosis, directional migration and chemotaxis. Our observations are then confirmed by in silico protein-protein interaction analysis.
Collectively, our results reveal that neutrophils drastically regulate their biochemical pathways after the early stages of surgical trauma, showing lower activity. This implies higher susceptibility of the trauma patients to infection and bystander tissues damage.
在临床情况下，创伤与高死亡率和高发病率相关。中性粒细胞在创伤后多器官功能衰竭的发展中起关键作用。
为了详细了解创伤后初级阶段中性粒细胞的激活情况，本研究从对照大鼠和手术创伤大鼠中分离出中性粒细胞。使用纳升液相色谱与串联质谱联用技术分析提取的蛋白质。
在我们的分析中总共鉴定出2924种大鼠中性粒细胞蛋白质，其中393种在对照组和创伤组之间存在差异调节。通过对手术创伤中上调的190种蛋白质进行功能通路分析，我们发现了与转录起始和蛋白质生物合成相关的蛋白质。另一方面，在手术创伤中下调的203种蛋白质中，我们发现免疫反应、蛋白酶体降解和肌动蛋白细胞骨架的蛋白质富集。总体而言，酶预测分析表明，受调节的酶直接参与中性粒细胞凋亡、定向迁移和趋化作用。我们的观察结果随后通过计算机模拟蛋白质-蛋白质相互作用分析得到证实。
总体而言，我们的结果表明，中性粒细胞在手术创伤早期后会大幅调节其生化途径，活性降低。这意味着创伤患者更容易感染和出现旁观者组织损伤。
