Regulated Shedding of Syndecan Ectodomains by Chemokines

Chemokines are chemotactic cytokines that govern multiple aspects of host defense Interest in chemokines has increased as a result of their emerging role in immune and inflammatory responses, hematopoeisis, HIV infection Chemokines mediate biological activities through activation of G-protein-coupled receptors (GPCRs) GAGs are long, linear, and heterogeneous sulfated polysaccharides that are generally closely associated with or immobilized on cell surfaces by attachment to protein cores, forming proteoglycans (PGs) Four chemokine subgroups have been named C, CC, CXC, or CX 3 C according to the number and spacing of cysteine residues Stromal cell-derived factor-1 (SDF-1/CXCL12), a CXC chemokine, constitutively expressed in a wide variety of tissues, binds to the GPCR CXCR4 CXCR4 also functions as a coreceptor for X4 HIV isolates[14] and SDF-1/CXCL12 blocks cellular entry of these isolates Optimal inhibition requires SDF-1 interaction with cell surface HS However, the SDF-1/CXCL12-CXCR4 axis is involved in other pathological processes: angiogenesis, invasiveness, migration, and proliferation of cancer cells Nevertheless, the pathophysiological roles of chemokine-GAG interactions have not yet been elucidated.