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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.<\/jats:p>","DOI":"10.3390\/ijms252313038","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T06:38:25Z","timestamp":1733294305000},"page":"13038","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Neutrophil Elastase Targets Select Proteins on Human Blood-Monocyte-Derived Macrophage Cell Surfaces"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9146-9898","authenticated-orcid":false,"given":"Nadia Tasnim","family":"Ahmed","sequence":"first","affiliation":[{"name":"School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apparao B.","family":"Kummarapurugu","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Richmond at VCU, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7347-3188","authenticated-orcid":false,"given":"Shuo","family":"Zheng","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Richmond at VCU, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze","family":"Bulut","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Richmond at VCU, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Virginia Commonwealth University (VCU), Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4437-0249","authenticated-orcid":false,"given":"Aashish","family":"Batheja","sequence":"additional","affiliation":[{"name":"School of Medicine, Virginia Commonwealth University (VCU), Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Hawkridge","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Virginia Commonwealth University (VCU), Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2437-2859","authenticated-orcid":false,"given":"Judith A.","family":"Voynow","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Richmond at VCU, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nri3600","article-title":"Alveolar macrophages: Plasticity in a tissue-specific context","volume":"14","author":"Hussell","year":"2014","journal-title":"Nat. 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