Chemokine–glycosaminoglycan interaction (Chemokine–GAG interaction)

Chemokine–glycosaminoglycan (GAG) interactions are fundamental biochemical processes where chemokines bind to linear polysaccharides, such as heparan sulfate, located on the cell surface and within the extracellular matrix (Handel et al., 2005). This binding is crucial for the immobilization of chemokines, allowing for the formation of haptotactic gradients that guide the directional migration of leukocytes to inflammatory sites (Proudfoot et al., 2003). Furthermore, GAGs facilitate the oligomerization of chemokines, which is often required for their in vivo activity, and protect them from proteolytic degradation (Monneau et al., 2016). In various diseases, including chronic inflammation and cancer, these interactions are dysregulated, promoting excessive immune cell recruitment and metastasis (Dyer et al., 2016). Therapeutic targeting of these interactions, primarily through GAG mimetics or modified chemokines, aims to disrupt the recruitment of inflammatory cells without interfering with the direct signaling through G-protein coupled receptors (GPCRs).

Other names

Chemokine-heparin interactionChemokine-heparan sulfate interactionChemokine-proteoglycan interactionChemokine-GAG binding

Competitive inhibition of chemokine binding to glycosaminoglycans, disruption of haptotactic gradients, and inhibition of chemokine oligomerization to prevent leukocyte recruitment.