HUMAN INTERLEUKIN-4 IS A GLYCOSAMINOGLYCAN-BINDING PROTEIN

Using different binding assays we examined the interaction of the cyto kine interleukin 4 (IL-4) with basement membrane, Equilibrium binding analysis revealed a high-affinity site characterized by a dissociation constant (K-d) of 0.3nM. This interaction was confirmed by native pol yacrylamide gel electrophoresis, which also indicated that the binding sites are composed of glycosaminoglycans (GAGs). In competition studi es, N-sulfated GAGs (heparin and heparan sulfate) displayed a higher a ffinity than other GAGs for IL-4, and therefore may constitute the phy siological ligand. Furthermore, the enzymatic and chemical cleavage of heparan sulfate demonstrated that only few peculiar domains (i.e. N-s ulfated rich sequences) within heparan sulfate chains, displayed a sig nificant affinity for IL-4. These data indicate a possible role of GAG s in storing IL-4 and modulating the cellular response to this cytokin e. (C) 1997 Academic Press Limited.