Cxcl1 monomer–dimer equilibrium controls neutrophil extravasation

Iliana I. León-Vega, Eduardo Vadillo, Hilda Vargas-Robles, Krishna Rajarathnam, Michael Schnoor

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)565-572
Number of pages8
JournalJournal of Leukocyte Biology
Volume115
Issue number3
DOIs
StatePublished - Mar 2024
Externally publishedYes

Keywords

  • Cxcl1 chemokine
  • Cxcr2 receptor
  • ERK signaling
  • arrest
  • diapedesis
  • extravasation
  • glycosaminoglycan
  • keratinocyte-derived chemokine
  • monomer–dimer equilibrium

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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