Cxcl1 monomer-dimer equilibrium controls neutrophil extravasation

© 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.permissionsoup.com..

The chemokine Cxcl1 plays a crucial role in recruiting neutrophils in response to infection. The early events in chemokine-mediated neutrophil extravasation involve a sequence of highly orchestrated steps including rolling, adhesion, arrest, and diapedesis. Cxcl1 function is determined by its properties of reversible monomer-dimer equilibrium and binding to Cxcr2 and glycosaminoglycans. Here, we characterized how these properties orchestrate extravasation using intravital microscopy of the cremaster. Compared to WT Cxcl1, which exists as both a monomer and a dimer, the trapped dimer caused faster rolling, less adhesion, and less extravasation. Whole-mount immunofluorescence of the cremaster and arrest assays confirmed these data. Moreover, the Cxcl1 dimer showed impaired LFA-1-mediated neutrophil arrest that could be attributed to impaired Cxcr2-mediated ERK signaling. We conclude that Cxcl1 monomer-dimer equilibrium and potent Cxcr2 activity of the monomer together coordinate the early events in neutrophil recruitment.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:115

Enthalten in:

Journal of leukocyte biology - 115(2024), 3 vom: 23. Feb., Seite 565-572

Sprache:

Englisch

Beteiligte Personen:

León-Vega, Iliana I [VerfasserIn]
Vadillo, Eduardo [VerfasserIn]
Vargas-Robles, Hilda [VerfasserIn]
Rajarathnam, Krishna [VerfasserIn]
Schnoor, Michael [VerfasserIn]

Links:

Volltext

Themen:

Arrest
Chemokine CXCL1
Chemokines
Cxcl1 chemokine
Cxcr2 receptor
Diapedesis
ERK signaling
Extravasation
Glycosaminoglycan
Glycosaminoglycans
Journal Article
Keratinocyte-derived chemokine
Monomer–dimer equilibrium
Receptors, Interleukin-8B
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 26.02.2024

Date Revised 05.03.2024

published: Print

Citation Status MEDLINE

doi:

10.1093/jleuko/qiad159

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366187732