Cargando…
Myeloperoxidase Negatively Regulates Neutrophil–Endothelial Cell Interactions by Impairing αMβ2 Integrin Function in Sterile Inflammation
Interactions of neutrophils with endothelial cells (ECs) and platelets contribute to tissue damage and vascular occlusion under sterile inflammatory conditions. However, the molecular mechanisms regulating the cell–cell interactions remain poorly understood. Previous studies suggest that reactive ox...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946029/ https://www.ncbi.nlm.nih.gov/pubmed/29780806 http://dx.doi.org/10.3389/fmed.2018.00134 |
_version_ | 1783322109292838912 |
---|---|
author | Tseng, Alan Kim, Kyungho Li, Jing Cho, Jaehyung |
author_facet | Tseng, Alan Kim, Kyungho Li, Jing Cho, Jaehyung |
author_sort | Tseng, Alan |
collection | PubMed |
description | Interactions of neutrophils with endothelial cells (ECs) and platelets contribute to tissue damage and vascular occlusion under sterile inflammatory conditions. However, the molecular mechanisms regulating the cell–cell interactions remain poorly understood. Previous studies suggest that reactive oxygen species, such as hydrogen peroxide (H(2)O(2)), produced from NADPH oxidase 2 play a critical role in platelet–neutrophil interactions by regulating the function of neutrophil αMβ2 integrin during sterile inflammation. In this study, we further demonstrate a crucial role for myeloperoxidase (MPO) in regulating the adhesive function of neutrophils through αMβ2 integrin. Using real-time fluorescence intravital microscopy and in vitro assays, we showed that loss of MPO promoted neutrophil–EC interactions and neutrophil emigration but did not affect neutrophil–platelet interactions under inflammatory conditions. Using genetic and pharmacologic approaches, we found that following agonist stimulation, MPO knockout (KO) neutrophils exhibited a significant increase in extracellular H(2)O(2) and surface level of αMβ2 integrin and that these effects were dependent on MPO activity. Our in vivo studies using an ischemia/reperfusion-induced hepatic inflammation model revealed that compared to wild-type mice, neutrophils from MPO KO mice—displayed a pro-migratory phenotype while ameliorating tissue damage. These results suggest that MPO plays a negative role in the adhesive and migratory function of neutrophils by impairing αMβ2 integrin function under sterile inflammatory conditions. |
format | Online Article Text |
id | pubmed-5946029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59460292018-05-18 Myeloperoxidase Negatively Regulates Neutrophil–Endothelial Cell Interactions by Impairing αMβ2 Integrin Function in Sterile Inflammation Tseng, Alan Kim, Kyungho Li, Jing Cho, Jaehyung Front Med (Lausanne) Medicine Interactions of neutrophils with endothelial cells (ECs) and platelets contribute to tissue damage and vascular occlusion under sterile inflammatory conditions. However, the molecular mechanisms regulating the cell–cell interactions remain poorly understood. Previous studies suggest that reactive oxygen species, such as hydrogen peroxide (H(2)O(2)), produced from NADPH oxidase 2 play a critical role in platelet–neutrophil interactions by regulating the function of neutrophil αMβ2 integrin during sterile inflammation. In this study, we further demonstrate a crucial role for myeloperoxidase (MPO) in regulating the adhesive function of neutrophils through αMβ2 integrin. Using real-time fluorescence intravital microscopy and in vitro assays, we showed that loss of MPO promoted neutrophil–EC interactions and neutrophil emigration but did not affect neutrophil–platelet interactions under inflammatory conditions. Using genetic and pharmacologic approaches, we found that following agonist stimulation, MPO knockout (KO) neutrophils exhibited a significant increase in extracellular H(2)O(2) and surface level of αMβ2 integrin and that these effects were dependent on MPO activity. Our in vivo studies using an ischemia/reperfusion-induced hepatic inflammation model revealed that compared to wild-type mice, neutrophils from MPO KO mice—displayed a pro-migratory phenotype while ameliorating tissue damage. These results suggest that MPO plays a negative role in the adhesive and migratory function of neutrophils by impairing αMβ2 integrin function under sterile inflammatory conditions. Frontiers Media S.A. 2018-05-04 /pmc/articles/PMC5946029/ /pubmed/29780806 http://dx.doi.org/10.3389/fmed.2018.00134 Text en Copyright © 2018 Tseng, Kim, Li and Cho. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Tseng, Alan Kim, Kyungho Li, Jing Cho, Jaehyung Myeloperoxidase Negatively Regulates Neutrophil–Endothelial Cell Interactions by Impairing αMβ2 Integrin Function in Sterile Inflammation |
title | Myeloperoxidase Negatively Regulates Neutrophil–Endothelial Cell Interactions by Impairing αMβ2 Integrin Function in Sterile Inflammation |
title_full | Myeloperoxidase Negatively Regulates Neutrophil–Endothelial Cell Interactions by Impairing αMβ2 Integrin Function in Sterile Inflammation |
title_fullStr | Myeloperoxidase Negatively Regulates Neutrophil–Endothelial Cell Interactions by Impairing αMβ2 Integrin Function in Sterile Inflammation |
title_full_unstemmed | Myeloperoxidase Negatively Regulates Neutrophil–Endothelial Cell Interactions by Impairing αMβ2 Integrin Function in Sterile Inflammation |
title_short | Myeloperoxidase Negatively Regulates Neutrophil–Endothelial Cell Interactions by Impairing αMβ2 Integrin Function in Sterile Inflammation |
title_sort | myeloperoxidase negatively regulates neutrophil–endothelial cell interactions by impairing αmβ2 integrin function in sterile inflammation |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946029/ https://www.ncbi.nlm.nih.gov/pubmed/29780806 http://dx.doi.org/10.3389/fmed.2018.00134 |
work_keys_str_mv | AT tsengalan myeloperoxidasenegativelyregulatesneutrophilendothelialcellinteractionsbyimpairingamb2integrinfunctioninsterileinflammation AT kimkyungho myeloperoxidasenegativelyregulatesneutrophilendothelialcellinteractionsbyimpairingamb2integrinfunctioninsterileinflammation AT lijing myeloperoxidasenegativelyregulatesneutrophilendothelialcellinteractionsbyimpairingamb2integrinfunctioninsterileinflammation AT chojaehyung myeloperoxidasenegativelyregulatesneutrophilendothelialcellinteractionsbyimpairingamb2integrinfunctioninsterileinflammation |