Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant.
GPCR
heterodimer
inflammation
leukocyte
proteoglycan
Journal
Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628
Informations de publication
Date de publication:
24 Nov 2023
24 Nov 2023
Historique:
received:
12
04
2023
revised:
26
07
2023
accepted:
01
08
2023
pmc-release:
01
12
2024
medline:
27
11
2023
pubmed:
25
8
2023
entrez:
25
8
2023
Statut:
ppublish
Résumé
Microbial infection is characterized by release of multiple proinflammatory chemokines that direct neutrophils to the insult site. How collective function of these chemokines orchestrates neutrophil recruitment is not known. Here, we characterized the role for heterodimer and show that the Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant in mice and can recruit more neutrophils than the individual chemokines. Chemokine-mediated neutrophil recruitment is determined by Cxcr2 receptor signaling, Cxcr2 endocytosis, and binding to glycosaminoglycans. We have now determined heterodimer's Cxcr2 activity using cellular assays and Cxcr2 density in blood and recruited neutrophils in heterodimer-treated mice. We have shown that the heterodimer binds glycosaminoglycans with higher affinity and more efficiently than Cxcl1 or Cxcl2. These data collectively indicate that optimal glycosaminoglycan interactions and dampened receptor activity acting in concert in a dynamic fashion promote heterodimer-mediated robust neutrophil recruitment. We propose that this could play a critical role in combating infection.
Identifiants
pubmed: 37625009
pii: 7251236
doi: 10.1093/jleuko/qiad097
pmc: PMC10673714
doi:
Substances chimiques
Chemokine CXCL1
0
Chemokines
0
Interleukin-8
0
Glycosaminoglycans
0
Chemokine CXCL2
0
Receptors, Interleukin-8B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
666-671Subventions
Organisme : NIAID NIH HHS
ID : R21 AI135606
Pays : United States
Organisme : NIH HHS
ID : R21AI124681
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Déclaration de conflit d'intérêts
Conflict of interest statement. None declared.
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