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

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.