Glycosaminoglycan–chemokine interaction (GAG–chemokine interaction)

Glycosaminoglycan–chemokine interactions refer to the binding of chemokines to linear, sulfated carbohydrate chains such as heparan sulfate, which are found on cell surfaces and within the extracellular matrix (PubMed: 22566230). This interaction is a critical regulatory step in the immune system, as it facilitates the immobilization and presentation of chemokines to their cognate G protein-coupled receptors on leukocytes (PMC: PMC7142145). By sequestering chemokines, glycosaminoglycans (GAGs) enable the formation of stable haptotactic gradients that guide directed cell migration from the blood into tissues (PLoS ONE: e104107). Furthermore, GAG binding can promote chemokine oligomerization, which is often essential for their in vivo biological activity and protection from proteolytic degradation (Biochemistry: 10.1021/bi00182a025). Dysregulation of these interactions is implicated in various pathological conditions, including chronic inflammation, autoimmune disorders, and cancer metastasis, where aberrant chemokine gradients drive excessive leukocyte infiltration or tumor cell spread (Front. Immunol.: 11:483). Consequently, the GAG–chemokine interface has emerged as a promising therapeutic target (Semin. Immunol.: 15(2):127-32). Drug development strategies include the use of GAG mimetics like muparfostat and pixatimod, which competitively inhibit chemokine binding, and Spiegelmers such as olaptesed pegol that sequester specific chemokines to prevent their interaction with GAGs (Pharmaceuticals: 10(3):70).

Other names

Chemokine-GAG interactionChemokine-glycosaminoglycan bindingChemokine-proteoglycan interactionChemokine-heparan sulfate interaction

Competitive inhibition of chemokine-GAG binding, sequestration of chemokines to prevent gradient formation, and disruption of chemokine presentation to receptors.