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Neutrophils and their granule enzymes, including neutrophil elastase, are key mediators of the pathophysiology of acute respiratory failure. Although intracellular neutrophil elastase functions as a host defensive factor against pathogens, its leakage into airway spaces induces degradation of host connective tissue components. This leakage disrupts host innate immune responses via proteolytic cleavage of Toll-like receptors and cytokines. Here, we investigated whether neutrophils possess proteases that cleave adaptive immune molecules. We found that expression of the human leukocyte antigen (HLA) class II molecule HLA-DP \u03b21 was decreased in THP-1-derived macrophages treated with supernatants from dead neutrophils. This decreased HLA-DP \u03b21 expression was counteracted by treatment with neutrophil elastase inhibitor, suggesting proteolytic cleavage of HLA-DP \u03b21 by neutrophil elastase. SDS-PAGE showed that neutrophil elastase cleaved recombinant HLA-DP \u03b11, -DP \u03b21, -DQ \u03b11, -DQ \u03b21, -DR \u03b1, and -DR \u03b21. Neutrophil elastase also cleaved HLA-DP \u03b21 on extracellular vesicles isolated from macrophages without triggering morphological changes. Thus, leakage of neutrophil elastase may disrupt innate immune responses, antigen presentation, and T cell activation. Additionally, inhibition of neutrophil elastase is a potential therapeutic option for treating bacterial and viral pneumonia.<\/jats:p>","DOI":"10.1038\/s41598-021-82212-5","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T06:04:39Z","timestamp":1611813879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia"],"prefix":"10.1038","volume":"11","author":[{"given":"Hisanori","family":"Domon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoki","family":"Maekawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihito","family":"Isono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Furuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikara","family":"Kaito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Terao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"82212_CR1","first-page":"252","volume":"107","author":"GM Matuschak","year":"2010","unstructured":"Matuschak, G. 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