Ahmed Nadia Tasnim, Kummarapurugu Apparao B, Zheng Shuo, Bulut Gamze, Kang Le, Batheja Aashish, Hawkridge Adam, Voynow Judith A
School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA 23298, USA.
Children's Hospital of Richmond at VCU, Richmond, VA 23298, USA.
Int J Mol Sci. 2024 Dec 4;25(23):13038. doi: 10.3390/ijms252313038.
Neutrophil elastase (NE) has been reported to be a pro-inflammatory stimulus for macrophages. The aim of the present study was to determine the impact of NE exposure on the human macrophage proteome and evaluate its impact on pro-inflammatory signals. Human blood monocytes from healthy volunteers were differentiated to macrophages and then exposed to either 500 nM of NE or control vehicle for 2 h in triplicate. Label-free quantitative proteomics analysis identified 41 differentially expressed proteins in the NE versus control vehicle datasets. A total of 26 proteins were downregulated and of those, 21 were cell surface proteins. Importantly, four of the cell surface proteins were proteoglycans: neuropilin 1 (), syndecan 2 (), glypican 4 (), and CD99 antigen-like protein 2 () along with neuropilin 2 (), CD99 antigen (), and endoglin () which are known interactors. Additional NE-targeted proteins related to macrophage function were also measured including , , , , and . Collectively, this study provides a comprehensive unbiased view of selective NE-targeted cell surface proteins in chronically inflamed lungs.
据报道，中性粒细胞弹性蛋白酶（NE）是巨噬细胞的一种促炎刺激物。本研究的目的是确定暴露于NE对人巨噬细胞蛋白质组的影响，并评估其对促炎信号的影响。将来自健康志愿者的人血单核细胞分化为巨噬细胞，然后一式三份地将其暴露于500 nM的NE或对照载体中2小时。无标记定量蛋白质组学分析在NE与对照载体数据集中鉴定出41种差异表达的蛋白质。共有26种蛋白质表达下调，其中21种是细胞表面蛋白质。重要的是，细胞表面蛋白质中的四种是蛋白聚糖：神经纤毛蛋白1（）、多功能蛋白聚糖2（）、磷脂酰肌醇蛋白聚糖4（）和CD99抗原样蛋白2（），以及已知的相互作用分子神经纤毛蛋白2（）、CD99抗原（）和内皮糖蛋白（）。还测量了与巨噬细胞功能相关的其他NE靶向蛋白，包括、、、和。总的来说，这项研究提供了对慢性炎症肺中选择性NE靶向细胞表面蛋白的全面、无偏见的看法。
