Cxcl1 monomer-dimer equilibrium controls neutrophil extravasation

J Leukoc Biol. 2023 Dec 21:qiad159. doi: 10.1093/jleuko/qiad159. Online ahead of print.ABSTRACTThe 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 - 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, that 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.PMID:38128116 | DOI:10.1093/jleuko/qiad159

Source: Journal of Leukocyte Biology - December 21, 2023 Category: Hematology Authors: Iliana I Le ón-Vega Eduardo Vadillo Hilda Vargas-Robles Krishna Rajarathnam Michael Schnoor Source Type: research