Glycan and glycosaminoglycan binding properties of stromal cell-derived factor (SDF)-1alpha

Abstract

We show here that cell surface glycosaminoglycans (GAGs) are involved in the binding of stromal cell-derived factor (SDF)-1alpha to CD4(+)lymphoid CEM or monocytic U937 cells, inasmuch as pretreating the cells with heparitinase or chondroitinase inhibits SDF-1alpha binding by 40-41% and 31-35%, respectively. Soluble heparin or chondroitin sulfate partially but significantly inhibits SDF-1alpha binding to the cells by 45-52% and 42-56%, respectively, while dextran has no significant effect. Taken together, these results indicate the role of GAGs in SDF-1alpha attachment to the cells. However, the effects of heparitinase and chondroitinase as well as those of heparin and chondroitin sulfate are not additive, which suggests that SDF-1alpha may attach to the cells through different GAGs, and also through other ligands. Soluble mannan also inhibits SDF-1alpha binding to the cells by 30-33%. Additivity between this effect and that of heparin or chondroitin sulfate is observed. Therefore, beside GAGs, mannose-containing species may also be involved in SDF-1alpha attachment to the cells. Accordingly, SDF-1alpha specifically binds to heparin-agarose and mannose-divinylsulfone agarose affinity matrices, and these interactions are inhibited respectively by soluble heparin, chondroitin sulfate, and mannan. We have previously shown that gp120 of X4 strain HIV-1LAI presents specific carbohydrate-binding properties for mannosylated derivatives, including mannan, and for GAGs including heparin. The present data therefore indicate that, in the same manner as HIV-1 Env, SDF-1alpha can interact with GAGs and glycans at the cell surface.

Structural and Functional Basis of CXCL12 (Stromal Cell-derived Factor-1α) Binding to Heparin

“…100 nM CXCL12 is inhibited by 10 and 100 g/ml of low molecular weight heparin with p Յ 0.0003 and by 10 and 100 g/ml of high molecular weight heparin with p Յ 0.0002. both 10 and 100 nM CXCL12. These data are in agreement with previous observations on the negative regulatory effects of soluble GAGs on in vitro binding of CXCL12 to various cell lines (40,41) and are consistent with a sequestration mechanism that prevents the interaction of the chemokine with the cell surface.…”

Proteoglycans on bone marrow endothelial cells bind and present SDF-1 towards hematopoietic progenitor cells

“…Others, however, have also reported SDF-1 binding via CS chains. 27 Treatment with both GAG-degrading enzymes did not result in complete inhibition of SDF-1 binding (65.6%), suggesting the presence of (an)other unknown trypsin-sensitive receptor(s) for SDF-1 or incomplete cleavage by the enzymes used. The latter seems unlikely as for each enzyme activity was tested.…”

“…In addition to GAGs, mannose-containing species could be involved in SDF-1 binding. 27 Using another anti-SDF-1 antibody MAB310, no cell surface expression of SDF-1 could be detected on the endothelial cells. In contrast, the cell line KG-1v with high CXCR4 levels showed high SDF-1 expression with this antibody.…”

“…SDF-1 has been reported by other groups to be able to bind to cellular proteoglycans (PGs). 26,27 PGs are macromolecules consisting of a core protein covalently attached to linear glycosaminoglycan (GAG) chains. These polysaccharide GAG chains consist of repeating disaccharide units.…”

Prolonged transendothelial migration of human haematopoietic stem and progenitor cells (HSPCs) towards hydrogel-released SDF1

“…Sulphated GAGs, in particular heparan sulphate, exhibit a particularly high affinity to SDF1 and have been reported to support presentation of SDF1 to the vascular lumen in the stem cell niche [16][17]30].…”