Adhesion Of Progenitor Cells Research Articles

Expression of Integrins and Examination of Their Adhesive Function in Normal and Leukemic Hematopoietic Cells

Adhesion of hematopoietic progenitor cells to marrow-derived adherent cells has been noted for erythroid, myeloid, and lymphoid precursors. In this report, we have characterized very late antigen (VLA) integrin expression on normal CD34+ marrow progenitors, on leukemic cell lines, and on blasts from patients with acute myelogenous or monocytic leukemias. CD34+ progenitor cells expressed the integrin beta 1 chain (CD29), VLA-4 alpha (CD49d), and VLA-5 alpha (CD49e). The myeloid lines KG1 and KG1a also expressed CD49d and CD49e as did the Mo7e megakaryoblastic line. CD29, CD18, and CD11a were also present on each of these cell lines. Only the Mo7e line expressed the cytoadhesins GPIIbIIIa or GPIb. Binding of KG1a to marrow stroma was partially inhibited by antibodies to CD49d and its ligand, vascular cell adhesion molecule (VCAM-1). The majority of leukemic blasts studied expressed CD49d and CD49e as well. Blasts from patients with acute myelomonocytic leukemia consistently bound to stroma at levels greater than 20%, and adhesion to stroma could in some cases be partly inhibited by anti-CD49d. No role for glycosylphosphatidyl-inositol (GPI)-linked structures was demonstrated in these binding assays because the adhesion of leukemic blasts to stroma was not diminished after treatment with phosphatidylinositol-specific phospholipase C (PI-PLC). These studies indicate that CD34+ myeloid progenitors, myeloid leukemic cell lines, and leukemic blasts possess a similar array of VLA integrins. Their functional importance individually or in combination with other mediators of attachment in adhesion, transendothelial migration, and differentiation has yet to be fully elucidated.

Lineage- and stage-specific adhesion of human hematopoietic progenitor cells to extracellular matrices from marrow fibroblasts

Local regulation of hematopoietic differentiation in the marrow requires close interactions with components of the microenvironment. In this study, we explored the capacity of human marrow hematopoietic progenitor cells to adhere in vitro to the extracellular matrix (ECM) secreted by human marrow fibroblasts. When marrow mononuclear cells were incubated on ECM-coated dishes, all types of progenitors adhered to this substrate through an active process requiring divalent cations and serum factors. The proportion of erythropoietic progenitors attached to ECM in two hours was at least twofold higher than that of granulopoietic progenitors. Moreover, in the erythroid lineage, the capacity to adhere to ECM increased with the degree of differentiation of the progenitor: 28% of CFU-E adhered to ECM as compared with 13% of immature BFU-E. Thus, ECM-mediated adherence varied both with the cell lineage and the maturation stage of the progenitor. Purified fibronectin could substitute for ECM in the adhesion assay, and ECM- mediated adhesion of CFU-E and BFU-E was partially inhibited by a polyclonal antifibronectin antibody, which implies that fibronectin may be one ECM component involved in progenitor cell adhesion. Incomplete inhibition of progenitor adhesion to ECM by the antifibronectin antibody, however, as well as the lower proportion of precursors attaching to purified fibronectin as compared with ECM suggest that other matrix molecules may also mediate erythroid progenitors attachment to ECM. These observations support the idea that hematopoietic progenitor cells may regulate their differentiation in part through the modulation of adhesive interactions with a number of constituents of the microenvironment.

Lineage- and Stage-Specific Adhesion of Human Hematopoietic Progenitor Cells to Extracellular Matrices From Marrow Fibroblasts

AbstractLocal regulation of hematopoietic differentiation in the marrow requires close interactions with components of the microenvironment. In this study, we explored the capacity of human marrow hematopoietic progenitor cells to adhere in vitro to the extracellular matrix (ECM) secreted by human marrow fibroblasts. When marrow mononuclear cells were incubated on ECM-coated dishes, all types of progenitors adhered to this substrate through an active process requiring divalent cations and serum factors. The proportion of erythropoietic progenitors attached to ECM in two hours was at least twofold higher than that of granulopoietic progenitors. Moreover, in the erythroid lineage, the capacity to adhere to ECM increased with the degree of differentiation of the progenitor: 28% of CFU-E adhered to ECM as compared with 13% of immature BFU-E. Thus, ECM-mediated adherence varied both with the cell lineage and the maturation stage of the progenitor. Purified fibronectin could substitute for ECM in the adhesion assay, and ECM-mediated adhesion of CFU-E and BFU-E was partially inhibited by a polyclonal antifibronectin antibody, which implies that fibronectin may be one ECM component involved in progenitor cell adhesion. Incomplete inhibition of progenitor adhesion to ECM by the antifibronectin antibody, however, as well as the lower proportion of precursors attaching to purified fibronectin as compared with ECM suggest that other matrix molecules may also mediate erythroid progenitors attachment to ECM. These observations support the idea that hematopoietic progenitor cells may regulate their differentiation in part through the modulation of adhesive interactions with a number of constituents of the microenvironment.1988 by Grune & Stratton, Inc. 0006-4971/88/7102-0003$3.00/0