Neutrophil Elastase Targets Select Proteins on Human Blood-Monocyte-Derived Macrophage Cell Surfaces

被引:1
|
作者
Ahmed, Nadia Tasnim [1 ]
Kummarapurugu, Apparao B. [2 ]
Zheng, Shuo [2 ]
Bulut, Gamze [2 ]
Kang, Le [3 ]
Batheja, Aashish [4 ]
Hawkridge, Adam [1 ]
Voynow, Judith A. [2 ]
机构
[1] Virginia Commonwealth Univ VCU, Sch Pharm, Richmond, VA 23298 USA
[2] VCU, Childrens Hosp Richmond, Richmond, VA 23298 USA
[3] Virginia Commonwealth Univ VCU, Dept Biostat, Richmond, VA 23298 USA
[4] Virginia Commonwealth Univ VCU, Sch Med, Richmond, VA 23298 USA
关键词
neutrophil elastase; ELANE; cystic fibrosis; COPD; macrophages; polarization; inflammation; proteoglycans; HUMAN-LEUKOCYTE ELASTASE; CYSTIC-FIBROSIS; NEUROPILIN-1; RECEPTOR; CD99; PROTEOGLYCANS; GLYPICAN-4; EXPRESSION; CLEAVAGE;
D O I
10.3390/ijms252313038
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (NRP1), syndecan 2 (SDC2), glypican 4 (GPC4), and CD99 antigen-like protein 2 (CD99L2) along with neuropilin 2 (NRP2), CD99 antigen (CD99), and endoglin (ENG) which are known interactors. Additional NE-targeted proteins related to macrophage function were also measured including CD40, CD48, SPINT1, ST14, and MSR1. Collectively, this study provides a comprehensive unbiased view of selective NE-targeted cell surface proteins in chronically inflamed lungs.
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页数:14
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