Heparan sulfate is necessary for adhesive interactions between human early hemopoietic progenitor cells and the extracellular matrix of the marrow microenvironment.
Human hemopoietic blast colony-forming cells (BI-CFCs) recognize and adhere to the extracellular matrix (ECM) produced by marrow-derived stromal cells in vitro. We have investigated the requirements for this interaction by testing the capacity of BI-CFCs to adhere to ECM components under a variety of conditions. Binding was prevented completely by prior treatment of stromal ECM with nitrous acid, in large part by treatment with heparitinase or hyaluronidase, and slightly by treatment with chondroitinases. Whereas heparan sulfate isolated from marrow stromal cultures effectively blocked binding, heparan sulfate from bovine kidney did not. Chondroitin sulfate and hyaluronic acid did not have any effect in this test. In contrast, collagen was not sufficient for the interaction because dishes coated with collagen type I or IV did not act as adhesive surfaces for BI-CFCs. Ligands for integrin receptors (e.g., fibronectin) did not participate in BI-CFC binding because the synthetic pentapeptide glycine-arginine-glycine-asparagine-serine did not compete with stroma in binding BI-CFCs. These findings indicate that heparan sulfate in the bone marrow microenvironment is necessary for BI-CFC binding to ECM and may contribute to localizing hemopoietic stem cells in hemopoietic tissue.
Gordon
M Y
MY
Leukaemia Research Fund Centre, Institute of Cancer Research, London, U.K.
Riley
G P
GP
Clarke
D
D
D000954:Antigens, Surface / Q000502:physiology*; D001667:Binding, Competitive; D001854:Bone Marrow Cells; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D006025:Glycosaminoglycans / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006497:Heparan Sulfate / Q000502:physiology*; D006801:Humans; D009842:Oligopeptides / Q000378:metabolism; D011485:Protein Binding
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D009842:Oligopeptides; C049554:glycyl-arginyl-glycyl-aspartyl-serine