Cargando…
Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury
Infiltration of polymorphonuclear neutrophils (PMNs) plays a central role in acute lung injury (ALI). The mechanisms governing PMN inflammatory responses, however, remain incompletely understood. Based on our recent study showing a non-metabolic role of pyruvate kinase type M2 (PKM2) in controlling...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138865/ https://www.ncbi.nlm.nih.gov/pubmed/35625931 http://dx.doi.org/10.3390/biomedicines10051193 |
_version_ | 1784714724804395008 |
---|---|
author | Sun, Xinlei Shi, Fujie Wang, Weiran Wu, Yunfei Qu, Shuang Li, Jing Liang, Hongwei Zen, Ke |
author_facet | Sun, Xinlei Shi, Fujie Wang, Weiran Wu, Yunfei Qu, Shuang Li, Jing Liang, Hongwei Zen, Ke |
author_sort | Sun, Xinlei |
collection | PubMed |
description | Infiltration of polymorphonuclear neutrophils (PMNs) plays a central role in acute lung injury (ALI). The mechanisms governing PMN inflammatory responses, however, remain incompletely understood. Based on our recent study showing a non-metabolic role of pyruvate kinase type M2 (PKM2) in controlling PMN degranulation of secondary and tertiary granules and consequent chemotaxis, here we tested a hypothesis that Pkm2-deficient mice may resist ALI due to impaired PMN inflammatory responses. We found that PMN aerobic glycolysis controlled the degranulation of secondary and tertiary granules induced by fMLP and PMA. Compared to WT PMNs, Pkm2-deficient (Pkm2(-/-)) PMNs displayed significantly less capacity for fMLP- or PMA-induced degranulation of secondary and tertiary granules, ROS production, and transfilter migration. In line with this, myeloid-specific Pkm2(-/-) mice exhibited impaired zymosan-induced PMN infiltration in the peritoneal cavity. Employing an LPS-induced ALI mouse model, LPS-treated Pkm2(-/-) mice displayed significantly less infiltration of inflammatory PMNs in the alveolar space and a strong resistance to LPS-induced ALI. Our results thus reveal that PKM2 is required for PMN inflammatory responses and deletion of PKM2 in PMN leads to an impaired PMN function but protection against LPS-induced ALI. |
format | Online Article Text |
id | pubmed-9138865 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91388652022-05-28 Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury Sun, Xinlei Shi, Fujie Wang, Weiran Wu, Yunfei Qu, Shuang Li, Jing Liang, Hongwei Zen, Ke Biomedicines Article Infiltration of polymorphonuclear neutrophils (PMNs) plays a central role in acute lung injury (ALI). The mechanisms governing PMN inflammatory responses, however, remain incompletely understood. Based on our recent study showing a non-metabolic role of pyruvate kinase type M2 (PKM2) in controlling PMN degranulation of secondary and tertiary granules and consequent chemotaxis, here we tested a hypothesis that Pkm2-deficient mice may resist ALI due to impaired PMN inflammatory responses. We found that PMN aerobic glycolysis controlled the degranulation of secondary and tertiary granules induced by fMLP and PMA. Compared to WT PMNs, Pkm2-deficient (Pkm2(-/-)) PMNs displayed significantly less capacity for fMLP- or PMA-induced degranulation of secondary and tertiary granules, ROS production, and transfilter migration. In line with this, myeloid-specific Pkm2(-/-) mice exhibited impaired zymosan-induced PMN infiltration in the peritoneal cavity. Employing an LPS-induced ALI mouse model, LPS-treated Pkm2(-/-) mice displayed significantly less infiltration of inflammatory PMNs in the alveolar space and a strong resistance to LPS-induced ALI. Our results thus reveal that PKM2 is required for PMN inflammatory responses and deletion of PKM2 in PMN leads to an impaired PMN function but protection against LPS-induced ALI. MDPI 2022-05-21 /pmc/articles/PMC9138865/ /pubmed/35625931 http://dx.doi.org/10.3390/biomedicines10051193 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sun, Xinlei Shi, Fujie Wang, Weiran Wu, Yunfei Qu, Shuang Li, Jing Liang, Hongwei Zen, Ke Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury |
title | Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury |
title_full | Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury |
title_fullStr | Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury |
title_full_unstemmed | Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury |
title_short | Myeloid-Specific Pyruvate-Kinase-Type-M2-Deficient Mice Are Resistant to Acute Lung Injury |
title_sort | myeloid-specific pyruvate-kinase-type-m2-deficient mice are resistant to acute lung injury |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138865/ https://www.ncbi.nlm.nih.gov/pubmed/35625931 http://dx.doi.org/10.3390/biomedicines10051193 |
work_keys_str_mv | AT sunxinlei myeloidspecificpyruvatekinasetypem2deficientmiceareresistanttoacutelunginjury AT shifujie myeloidspecificpyruvatekinasetypem2deficientmiceareresistanttoacutelunginjury AT wangweiran myeloidspecificpyruvatekinasetypem2deficientmiceareresistanttoacutelunginjury AT wuyunfei myeloidspecificpyruvatekinasetypem2deficientmiceareresistanttoacutelunginjury AT qushuang myeloidspecificpyruvatekinasetypem2deficientmiceareresistanttoacutelunginjury AT lijing myeloidspecificpyruvatekinasetypem2deficientmiceareresistanttoacutelunginjury AT lianghongwei myeloidspecificpyruvatekinasetypem2deficientmiceareresistanttoacutelunginjury AT zenke myeloidspecificpyruvatekinasetypem2deficientmiceareresistanttoacutelunginjury |