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 (<i>NRP1</i>), syndecan 2 (<i>SDC2</i>), glypican 4 (<i>GPC4</i>), and CD99 antigen-like protein 2 (<i>CD99L2</i>) along with neuropilin 2 (<i>NRP2</i>), CD99 antigen (<i>CD99</i>), and endoglin (<i>ENG</i>) which are known interactors. Additional NE-targeted proteins related to macrophage function were also measured including <i>CD40</i>, <i>CD48</i>, <i>SPINT1</i>, <i>ST14</i>, and <i>MSR1</i>. Collectively, this study provides a comprehensive unbiased view of selective NE-targeted cell surface proteins in chronically inflamed lungs.