Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant.

Autor:	Sawant KV; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States., Sepuru KM; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States., Penaranda B; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States., Lowry E; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States., Garofalo RP; Department of Pediatrics, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States.; Institute for Human Infections and Immunity, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States., Rajarathnam K; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States.; Institute for Human Infections and Immunity, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States.; Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, United States.
Jazyk:	angličtina
Zdroj:	Journal of leukocyte biology [J Leukoc Biol] 2023 Nov 24; Vol. 114 (6), pp. 666-671.
DOI:	10.1093/jleuko/qiad097
Abstrakt:	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. Competing Interests: Conflict of interest statement. None declared. (© 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.)
Databáze:	MEDLINE
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