Human CXCL6(6-77) (GCP-2, Granulocyte Chemotactic Protein-2) is a 72 amino acid chemokine involved in immune and inflammatory responses. Primarily secreted by macrophages, epithelial cells, and mesenchymal cells, CXCL6 attracts neutrophils by binding to CXCR1 and CXCR2 receptors, promoting their migration to sites of infection or injury. It also binds the scavenger receptor ACKR1. CXCL6 plays a role in host defense, wound healing, and tissue repair but is also implicated in pathological conditions like chronic inflammation and cancer, where it can enhance tumor growth and angiogenesis. Structurally similar to CXCL5, CXCL6 is notable for its potent neutrophil-activating properties. Full-length CXCL6 can be cleaved at the amino terminus by the membrane associated dipeptidyl-peptidase IV producing a 3-77 variant that is equally potent to full-length as a neutrophil chemoattractant. Additionally, a naturally produced 6-77 variant is also an equipotent chemoattractant for neutrophils.
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