Cargando…
Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis
Dysregulated chronic inflammation plays a crucial role in the pathophysiology of atherosclerosis and may be a result of impaired resolution. Thus, restoring levels of specialized pro‐resolving mediators (SPMs) to promote the resolution of inflammation has been proposed as a therapeutic strategy for...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305188/ https://www.ncbi.nlm.nih.gov/pubmed/35104001 http://dx.doi.org/10.1096/fj.202101219RR |
_version_ | 1784752265290055680 |
---|---|
author | Kraft, Jamie D. Blomgran, Robert Bergström, Ida Soták, Matúš Clark, Madison Rani, Alankrita Rajan, Meenu Rohini Dalli, Jesmond Nyström, Sofia Quiding‐Järbrink, Marianne Bromberg, Jonathan Skoog, Per Börgeson, Emma |
author_facet | Kraft, Jamie D. Blomgran, Robert Bergström, Ida Soták, Matúš Clark, Madison Rani, Alankrita Rajan, Meenu Rohini Dalli, Jesmond Nyström, Sofia Quiding‐Järbrink, Marianne Bromberg, Jonathan Skoog, Per Börgeson, Emma |
author_sort | Kraft, Jamie D. |
collection | PubMed |
description | Dysregulated chronic inflammation plays a crucial role in the pathophysiology of atherosclerosis and may be a result of impaired resolution. Thus, restoring levels of specialized pro‐resolving mediators (SPMs) to promote the resolution of inflammation has been proposed as a therapeutic strategy for patients with atherosclerosis, in addition to standard clinical care. Herein, we evaluated the effects of the SPM lipids, lipoxin A(4) (LXA(4)) and lipoxin B(4) (LXB(4)), on neutrophils isolated from patients with atherosclerosis compared with healthy controls. Patients displayed altered endogenous SPM production, and we demonstrated that lipoxin treatment in whole blood from atherosclerosis patients attenuates neutrophil oxidative burst, a key contributor to atherosclerotic development. We found the opposite effect in neutrophils from healthy controls, indicating a potential mechanism whereby lipoxins aid the endogenous neutrophil function in health but reduce its excessive activation in disease. We also demonstrated that lipoxins attenuated upregulation of the high‐affinity conformation of the CD11b/CD18 integrin, which plays a central role in clot activation and atherosclerosis. Finally, LXB(4) enhanced lymphatic transmigration of human neutrophils isolated from patients with atherosclerosis. This finding is noteworthy, as impaired lymphatic function is now recognized as an important contributor to atherosclerosis. Although both lipoxins modulated neutrophil function, LXB(4) displayed more potent effects than LXA(4) in humans. This study highlights the therapeutic potential of lipoxins in atherosclerotic disease and demonstrates that the effect of these SPMs may be specifically tailored to the need of the individual. |
format | Online Article Text |
id | pubmed-9305188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93051882022-07-28 Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis Kraft, Jamie D. Blomgran, Robert Bergström, Ida Soták, Matúš Clark, Madison Rani, Alankrita Rajan, Meenu Rohini Dalli, Jesmond Nyström, Sofia Quiding‐Järbrink, Marianne Bromberg, Jonathan Skoog, Per Börgeson, Emma FASEB J Research Articles Dysregulated chronic inflammation plays a crucial role in the pathophysiology of atherosclerosis and may be a result of impaired resolution. Thus, restoring levels of specialized pro‐resolving mediators (SPMs) to promote the resolution of inflammation has been proposed as a therapeutic strategy for patients with atherosclerosis, in addition to standard clinical care. Herein, we evaluated the effects of the SPM lipids, lipoxin A(4) (LXA(4)) and lipoxin B(4) (LXB(4)), on neutrophils isolated from patients with atherosclerosis compared with healthy controls. Patients displayed altered endogenous SPM production, and we demonstrated that lipoxin treatment in whole blood from atherosclerosis patients attenuates neutrophil oxidative burst, a key contributor to atherosclerotic development. We found the opposite effect in neutrophils from healthy controls, indicating a potential mechanism whereby lipoxins aid the endogenous neutrophil function in health but reduce its excessive activation in disease. We also demonstrated that lipoxins attenuated upregulation of the high‐affinity conformation of the CD11b/CD18 integrin, which plays a central role in clot activation and atherosclerosis. Finally, LXB(4) enhanced lymphatic transmigration of human neutrophils isolated from patients with atherosclerosis. This finding is noteworthy, as impaired lymphatic function is now recognized as an important contributor to atherosclerosis. Although both lipoxins modulated neutrophil function, LXB(4) displayed more potent effects than LXA(4) in humans. This study highlights the therapeutic potential of lipoxins in atherosclerotic disease and demonstrates that the effect of these SPMs may be specifically tailored to the need of the individual. John Wiley and Sons Inc. 2022-02-01 2022-03 /pmc/articles/PMC9305188/ /pubmed/35104001 http://dx.doi.org/10.1096/fj.202101219RR Text en © 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Kraft, Jamie D. Blomgran, Robert Bergström, Ida Soták, Matúš Clark, Madison Rani, Alankrita Rajan, Meenu Rohini Dalli, Jesmond Nyström, Sofia Quiding‐Järbrink, Marianne Bromberg, Jonathan Skoog, Per Börgeson, Emma Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis |
title | Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis |
title_full | Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis |
title_fullStr | Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis |
title_full_unstemmed | Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis |
title_short | Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis |
title_sort | lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305188/ https://www.ncbi.nlm.nih.gov/pubmed/35104001 http://dx.doi.org/10.1096/fj.202101219RR |
work_keys_str_mv | AT kraftjamied lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT blomgranrobert lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT bergstromida lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT sotakmatus lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT clarkmadison lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT ranialankrita lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT rajanmeenurohini lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT dallijesmond lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT nystromsofia lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT quidingjarbrinkmarianne lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT brombergjonathan lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT skoogper lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis AT borgesonemma lipoxinsmodulateneutrophiloxidativeburstintegrinexpressionandlymphatictransmigrationdifferentiallyinhumanhealthandatherosclerosis |