Human interleukin 4 is a glycosaminoglycan-binding protein.

Using different binding assays we examined the interaction of the cytokine interleukin 4 (IL-4) with basement membrane. Equilibrium binding analysis revealed a high-affinity site characterized by a dissociation constant (Kd) of 0.3 nM. This interaction was confirmed by native polyacrylamide gel electrophoresis, which also indicated that the binding sites are composed of glycosaminoglycans (GAGs). In competition studies, N-sulfated GAGs (heparin and heparan sulfate) displayed a higher affinity than other GAGs for IL-4, and therefore may constitute the physiological ligand. Furthermore, the enzymatic and chemical cleavage of heparan sulfate demonstrated that only few peculiar domains (i.e. N-sulfated rich sequences) within heparan sulfate chains, displayed a significant affinity for IL-4. These data indicate a possible role of GAGs in storing IL-4 and modulating the cellular response to this cytokine.