Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia

Abstract Bacterial and viral respiratory infections can initiate acute lung injury and acute respiratory distress syndrome. Neutrophils and their granule enzymes, including neutrophil elastase, are key mediators of the pathophysiology of acute respiratory failure. Although intracellular neutrophil e...

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Autores principales:	Hisanori Domon, Tomoki Maekawa, Toshihito Isono, Kazuyuki Furuta, Chikara Kaito, Yutaka Terao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e061a8128da47aa84b0502e11573205
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spelling	oai:doaj.org-article:9e061a8128da47aa84b0502e115732052021-12-02T10:47:54ZProteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia10.1038/s41598-021-82212-52045-2322https://doaj.org/article/9e061a8128da47aa84b0502e115732052021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82212-5https://doaj.org/toc/2045-2322Abstract Bacterial and viral respiratory infections can initiate acute lung injury and acute respiratory distress syndrome. 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 β1 was decreased in THP-1-derived macrophages treated with supernatants from dead neutrophils. This decreased HLA-DP β1 expression was counteracted by treatment with neutrophil elastase inhibitor, suggesting proteolytic cleavage of HLA-DP β1 by neutrophil elastase. SDS-PAGE showed that neutrophil elastase cleaved recombinant HLA-DP α1, -DP β1, -DQ α1, -DQ β1, -DR α, and -DR β1. Neutrophil elastase also cleaved HLA-DP β1 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.Hisanori DomonTomoki MaekawaToshihito IsonoKazuyuki FurutaChikara KaitoYutaka TeraoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hisanori Domon Tomoki Maekawa Toshihito Isono Kazuyuki Furuta Chikara Kaito Yutaka Terao Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia
description	Abstract Bacterial and viral respiratory infections can initiate acute lung injury and acute respiratory distress syndrome. 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 β1 was decreased in THP-1-derived macrophages treated with supernatants from dead neutrophils. This decreased HLA-DP β1 expression was counteracted by treatment with neutrophil elastase inhibitor, suggesting proteolytic cleavage of HLA-DP β1 by neutrophil elastase. SDS-PAGE showed that neutrophil elastase cleaved recombinant HLA-DP α1, -DP β1, -DQ α1, -DQ β1, -DR α, and -DR β1. Neutrophil elastase also cleaved HLA-DP β1 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.
format	article
author	Hisanori Domon Tomoki Maekawa Toshihito Isono Kazuyuki Furuta Chikara Kaito Yutaka Terao
author_facet	Hisanori Domon Tomoki Maekawa Toshihito Isono Kazuyuki Furuta Chikara Kaito Yutaka Terao
author_sort	Hisanori Domon
title	Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia
title_short	Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia
title_full	Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia
title_fullStr	Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia
title_full_unstemmed	Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia
title_sort	proteolytic cleavage of hla class ii by human neutrophil elastase in pneumococcal pneumonia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9e061a8128da47aa84b0502e11573205
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Proteolytic cleavage of HLA class II by human neutrophil elastase in pneumococcal pneumonia

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