Role of heparan sulfate in mediating CXCL8-induced endothelial cell migration

Abstract

CXCL8 (Interleukin-8, IL-8) plays an important role in angiogenesis and wound heal- ing by prompting endothelial cell migration. It has been suggested that heparan sul- fate (HS) could provide binding sites on endothelial cells to retain and activate highly diffusible cytokines and inflammatory chemokines. In the present study, we aimed to test the hypothesis that HS is essential for enhancement of endothelial cell migration by CXCL8, and to explore the underlying mechanism by detecting the changes in ex- pression and activity of Rho GTPases and in the organization of actin cytoskeleton af- ter enzymatic removal of HS on human umbilical vein endothelial cells (HUVECs) by using heparinase III. Our results revealed that the wound healing induced by CXCL8 was greatly attenuated by removal of HS. The CXCL8-upregulated Rho GTPases in- cluding Cdc42, Rac1, and RhoA, and CXCL8-increased Rac1/Rho activity were sup- pressed by removal of HS. The polymerization and polarization of actin cytoskeleton, and the increasing of stress fibers induced by CXCL8 were also abolished by hepari- nase III. Taken together, our results demonstrated an essential role of HS in mediating CXCL8-induced endothelial cell migration, and highlighted the biological importance of the interaction between CXCL8 and heparan sulfate in wound healing.