Chemokine and Cellular Adhesion in the Context of Heparan Sulfate Proteoglycan

Abstract

Cytokines are diffusible and soluble factors with pleiotropic actions. However, heparan sulfate proteoglycan (HS-PG) on either the cell surface or matrices provides the following advantages to the function of heparin-binding cytokines such as chemokines, by immobilizing them and presents cytokines to their receptors on target cells: 1) HS-PG promotes the accumulation of cytokines at high concentration by binding them on the appropriate location where they encounter their target cells; 2) HS-PG protects cytokines from both chemical and physiological stimuli; 3) HS-PG induces conformation-dependent association of the cell surface molecules by binding them. Furthermore, interactions between HS-PG and cytokines promotes the assembly of the appropriate molecular complex to initiate signal transduction, because many of them are highly specific, and variation in the HS-PG determines the specificity of binding of cytokines. HS-PG thereby appears to play a pivotal role in the promotion and regulation of the multicrine regulatory mechanisms of particular cytokine functions, which allows for the regulated paracrine, autocrine, juxtacrine and matricrine stimulation of heparin-binding cytokines. Such multicrine-type cytokine functions mediated by HS-PG-binding efficiently facilitates regulated cellular interactions through cytokines as well as adhesion molecules, which is relevant not only to the process of leukemic cell infiltration and tumor metastasis, but also to the regulation of inflammation and leukocyte trafficking.