Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage.
Aging
/ immunology
Animals
Biological Transport
/ immunology
Chemokine CXCL1
/ immunology
Endothelial Cells
/ immunology
Endothelium, Vascular
/ immunology
Female
Inflammation
/ immunology
Intercellular Junctions
/ immunology
Lung
/ immunology
Male
Mice
Mice, Inbred C57BL
Neutrophils
/ immunology
Receptors, Interleukin-8B
/ immunology
Venules
/ immunology
ACKR1
CXCR2
Neutrophils
aging
chemokines
diapedesis
endothelium
extravasation
inflammation
mast cells
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
13 07 2021
13 07 2021
Historique:
received:
09
10
2020
revised:
11
03
2021
accepted:
27
04
2021
pubmed:
26
5
2021
medline:
15
9
2021
entrez:
25
5
2021
Statut:
ppublish
Résumé
Aging is associated with dysregulated immune functions. Here, we investigated the impact of age on neutrophil diapedesis. Using confocal intravital microscopy, we found that in aged mice, neutrophils adhered to vascular endothelium in inflamed tissues but exhibited a high frequency of reverse transendothelial migration (rTEM). This retrograde breaching of the endothelium by neutrophils was governed by enhanced production of the chemokine CXCL1 from mast cells that localized at endothelial cell (EC) junctions. Increased EC expression of the atypical chemokine receptor 1 (ACKR1) supported this pro-inflammatory milieu in aged venules. Accumulation of CXCL1 caused desensitization of the chemokine receptor CXCR2 on neutrophils and loss of neutrophil directional motility within EC junctions. Fluorescent tracking revealed that in aged mice, neutrophils undergoing rTEM re-entered the circulation and disseminated to the lungs where they caused vascular leakage. Thus, neutrophils stemming from a local inflammatory site contribute to remote organ damage, with implication to the dysregulated systemic inflammation associated with aging.
Identifiants
pubmed: 34033752
pii: S1074-7613(21)00187-4
doi: 10.1016/j.immuni.2021.04.025
pmc: PMC8284598
pii:
doi:
Substances chimiques
Chemokine CXCL1
0
Receptors, Interleukin-8B
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1494-1510.e7Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/14/3/30518
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/17/85/33395
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 098291/Z/12/Z
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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