title: Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma.
abstract: Hematopoietic stem cell interaction with elements of the underlying stroma is essential for sustained normal hematopoiesis. Here we have determined that adhesion receptors in the integrin family play a role in promoting adhesion of human hematopoietic stem cells to cultured human marrow stromal cells. Enriched CD34hi progenitor cells expressed VLA-4, VLA-5, and at least one or more beta 2 integrins. Homogeneous marrow stromal cell monolayers capable of supporting proliferation of cocultivated CD34hi cells expressed VCAM-1 and fibronectin (ligands for VLA-4 and VLA-5) as well as ICAM-1 (ligand for LFA-1 and Mac-1). Adhesion-blocking experiments indicated that VLA-4/VCAM-1, VLA-5/fibronectin, and beta 2-integrin/ICAM-1 pathways all are important for CD34hi cell attachment to stromal cells. Consistent with this suggestion, IL-1 stimulation of stromal cells caused both increased VCAM-1 and ICAM-1 expression and increased attachment by CD34hi bone marrow cells. In addition, CD34hi cells utilized VLA-4 to adhere to purified VCAM-1 and employed VLA-5 (and to a lesser extent VLA-4) to adhere to purified fibronectin. Together these results suggest that CD34hi stem cells may utilize multiple integrin-mediated adhesion pathways to localize within specialized microenvironmental niches created by marrow stromal cells.
authors.affiliation: Department of Tumor Virology, Dana Farber Cancer Institute, Boston, Massachusetts 02115.
authors.forename: J
authors.initials: J
authors.lastname: Teixidó
authors.forename: M E
authors.initials: ME
authors.lastname: Hemler
authors.forename: J S
authors.initials: JS
authors.lastname: Greenberger
authors.forename: P
authors.initials: P
authors.lastname: Anklesaria
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D018952:Antigens, CD34; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001854:Bone Marrow Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000502:physiology*; D011990:Receptors, Transferrin; D016029:Receptors, Very Late Antigen / Q000378:metabolism; D063268:Sialic Acid Binding Ig-like Lectin 3; D019010:Vascular Cell Adhesion Molecule-1
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000944:Antigens, Differentiation, B-Lymphocyte; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; C068126:CD71 antigen; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016023:Integrins; D011990:Receptors, Transferrin; D016029:Receptors, Very Late Antigen; D063268:Sialic Acid Binding Ig-like Lectin 3; D019010:Vascular Cell Adhesion Molecule-1