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

Abstract

We 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.

Influence of cell cycling and cell division on transendothelial migration of CD34+ cells

“…Such changes coincide with a reduction in adhesion to stroma and extracellular matrix components, thus providing a basis for the impaired engraftment of cytokine-stimulated cells. These findings, however, have not been confirmed in the human system, in which cytokine stimulation appears to enhance adhesion of CD34 + cells to stromal cells and fibronectin (Levesque et al, 1996;Yamaguchi et al, 1998), this effect being most marked for cells in S+G 2 /M; a finding which we have confirmed here. Furthermore, VLA-4 expression is increased on cells in S+G 2 /M phase of the cells cycle compared with cells in G 0 /G 1 , a finding confirmed by us and others (this work, and Fruehauf et al, 1998).…”

Phenotypic and functional characteristics of CD34+ cells are related to their anatomical environment: is their versatility a prerequisite for their bio-availability?

“…The higher proportion of cycling cells [10] and tyrosine phosphorylation level, which we observed in SSBM as compared with circulating CD34 ϩ cells, is in agreement with these results. It has been reported that quiescent CD34 ϩ cells adhered less efficiently to stroma than cycling cells, likely contributing to their higher circulation [3]. Such a superior migratory ability of G 0 /G 1 CD34 ϩ cells may have important implication for their homing and engraftment [20].…”

“…Their presence in low number in the PB from normal, unmobilized subjects demonstrates their continuous circulation under physiological conditions [1]. Unlike the numerous papers reporting data on HP from mPB, few groups have searched for the existence of a potential relationship between the phenotypic and functional characteristics of unmobilized circulating HP and those of their medullar sedentary counterparts [2][3][4][5]. Recent papers have underlined the crucial role of membrane receptors for cytokines and chemokines as well as of adhesion molecules in the circulation of hematopoietic cells [5][6][7].…”

The Role of Cytokines and Adhesion Molecules for Mobilization of Peripheral Blood Stem Cells

“…Circulating CD34 + cells express VLA-4 at a lower level when compared with CD34 + cells residing in the BM. This finding suggests that the release of CD34 + cells and the ability to circulate is related to the presence and expression level of VLA-4 [57,65,[69][70][71][72]. This view is supported by the finding that systemic treatment of primates and mice with monoclonal antibodies directed against VLA-4 resulted in a significant increase of circulating hematopoietic progenitor cells [73][74][75][76].…”