CXCL2型
CXCL1型
趋化因子受体
趋化因子
细胞生物学
生物
趋化性
趋化因子受体
免疫学
CXCL14型
促炎细胞因子
受体
炎症
生物化学
作者
Kirti V. Sawant,Krishna Mohan Sepuru,Brigith Penaranda,Emily R. Lowry,Robert Garofalo,Krishna Rajarathnam
标识
DOI:10.1093/jleuko/qiad097
摘要
Abstract 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.
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