Role of beta 1 and beta 2 integrins in the adhesion of human CD34hi stem cells to bone marrow stroma.
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.
Teixidó
J
J
Department of Tumor Virology, Dana Farber Cancer Institute, Boston, Massachusetts 02115.
Hemler
M E
ME
Greenberger
J S
JS
Anklesaria
P
P
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
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