INFLUENCE OF INTERLEUKIN-3 AND OTHER GROWTH-FACTORS ON ALPHA(4)BETA(1) INTEGRIN-MEDIATED ADHESION AND MIGRATION OF HUMAN HEMATOPOIETIC PROGENITOR CELLS

The mechanisms by which hematopoietic progenitor cells are normally an chored in stromal niches and yet can be mobilized by specific growth f actors are pearly understood. It is likely, however, that integrins an d their extracellular matrix (ECM) ligands play a key role in this pro cess, and recent evidence suggests that integrin function is modulated by signals originating from activated growth factor receptors. We hav e now examined this further by studying the role of growth factors on alpha(4) beta(1) integrin-mediated adhesion of human CD34(+) hematopoi etic progenitor cells to specific recombinant fibronectin fragments co ated onto tissue culture dishes. Cells were prepared from cord blood a nd peripheral blood harvests. During a 30-minute adhesion assay a mean of 74% of CD34 cells attached to the so-called H120 fragment of fibro nectin, which contains the strongest alpha(4) beta(1) integrin-binding sequence. The level of cell adhesion was significantly reduced by low concentrations of interleukin-a (IL-3) [2.5 to 10 ng/mL), whereas ste m cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) at these concentrations did not affect adherence of the cells, Migrato ry behavior of CD34 cells was examined using fibronectin fragments ads orbed onto a Transwell filter, The H120 fragment supported much higher levels of cell migration than the H0 fragment of fibronectin, which c ontains a weak alpha(4) beta(1) integrin binding sequence, Over a 16-h our assay, migration of peripheral blood progenitor cells was increase d slightly by SCF and by G-CSF. However, a marked stimulation was obse rved with IL-3, which significantly increased migration, Similar effec ts were noted with cord blood cells, although a small proportion of ce lls were able to migrate in the absence of growth factors, These resul ts indicate that there is a highly selective and functional link betwe en the alpha(4) beta(1) integrin and lL-3/IL-3-receptor that could aff ect the position of stem and progenitor cells in the marrow stroma and influence their growth and development. (C) 1997 by The American Soci ety of Hematology.