Adhesion Of CD34 Research Articles

Different Adhesive Characteristics and VLA-4 Expression of CD34+ Progenitors in G0/G1 Versus S+G2/M Phases of the Cell Cycle

AbstractWe identified the cell cycle status of CD34+ cells of steady-state bone marrow (BM) and peripheral blood (PB) obtained from healthy volunteers, and those of apherasis PB samples collected from healthy donors who had been administered granulocyte colony-stimulating factor (G-CSF). More than 10% of CD34+ cells in BM were in S+G2/M phase. In contrast, regardless of whether G-CSF treatment was performed, less than 2% of CD34+ cells in PB were cycling. BM CD34+ cells showed greater VLA-4 expression and adherence to stromal cells than PB CD34+cells. In addition, when cycling and dormant BM CD34+cells were analyzed separately, the cells in S+G2/M phase expressed more VLA-4 and adhered to the stromal cell monolayer more efficiently than the cells in G0/G1 phase. Furthermore, this adhesion of CD34+ cells to the stromal cell layer was almost completely inhibited by anti-VLA-4 antibody. Taken together, these results suggest that CD34+ progenitors in G0/G1 phase of the cell cycle differ from those in S+G2/M phase in adhesiveness mediated by VLA-4 in the hematopoietic microenvironment.© 1998 by The American Society of Hematology.

Signals from platelet/endothelial cell adhesion molecule enhance the adhesive activity of the very late antigen-4 integrin of human CD34+ hemopoietic progenitor cells.

Adhesive interactions between human CD34+ hemopoietic progenitor cells and bone marrow stromal cells control the localization, proliferation, and differentiation of CD34+ cells. Changes in adhesive interactions may contribute to the mobilization of CD34+ cells to the blood induced by chemotherapy and cytokines. Thus, the identities and functional states of adhesion receptors are critical properties of CD34+ cells. Here, we confirm that the adhesion receptors very late antigen-4 (VLA-4), LFA-1, and platelet/endothelial cell adhesion molecule-1 (PECAM-1) are expressed on the CD34+ cell line KG1a and on CD34+ normal, steady state bone marrow cells. Therapeutically mobilized CD34+ cells express similar levels of PECAM-1 but reduced levels of VLA-4 and LFA-1 in comparison with steady state bone marrow cells. Integrin adhesive activity was measured from the binding of PKH 26- or phycoerythrin-labeled CD34+ cells to FITC-labeled Chinese hamster ovary (CHO) cells expressing vascular CAM-1 (VCAM-1) or intercellular CAM-1, which are ligands for VLA-4 and LFA-1, respectively. Incubation mixtures were analyzed by flow cytometry for the loss of free CD34+ cells and gain of CD34(+)-CHO cell aggregates. VLA-4 mediates the strong and specific adhesion of KG1a cells and bone marrow CD34+ cells to VCAM-1-transfected CHO cells. CD34+ cells mobilized with granulocyte colony stimulating factor (G-CSF) or cyclophosphamide also bind VCAM-1 via VLA-4. The VLA-4-mediated adhesion of all CD34+ cells to VCAM-1 is enhanced by Abs to the coexpressed adhesion receptor PECAM-1, implicating signals transmitted from PECAM-1 as determinants of VLA-4 integrin activity. VLA-4 function in CD34+ cells mobilized with G-CSF or cyclophosphamide is equivalent to steady state CD34+ cells. LFA-1 mediates minimal adhesion between CD34+ cells and intercellular CAM-1 transfected CHO cells and is refractory to PECAM-1 modulation. We infer that VLA-4, but not LFA-1, contributes to the constitutive adhesive phenotype of CD34+ cells. PECAM-1 is probably one of several receptors that control adhesive interactions between hemopoietic progenitors and target cells by regulating the activation states of specific integrins.