title: TGF-beta and MIP-1 alpha exert their main inhibitory activity on very primitive CD34+2CD38- cells but show opposite effects on more mature CD34+CD38+ human hematopoietic progenitors.
abstract: We investigated the effects of transforming growth factor-beta (TGF-beta) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) on very primitive CD34++CD38- and on more mature CD34++CD38+ human hematopoietic progenitor cells by means of a two stage pre-colony-forming cell (pre-CFC) assay. The first (liquid) stage of this assay allows evaluation of the effects of TGF-beta and MIP-1 alpha on the "primary" proliferation of the progenitors under study and on the generation of "secondary" colony-forming cells (CFC, cells for which a second stage semisolid clonogenic assay was used as a read-out). TGF-beta inhibited the proliferation and CFC generation of CD34++CD38- and CD34+CD38+ cells, showing the strongest inhibitory activity on CD34++CD38- cells. MIP-1 alpha exerted a weaker inhibitory activity on CD34+2CD38- cells, whereas it enhanced the primary proliferation of CD34+CD38+ cells and generation of secondary CFC in this subpopulation. Thus, TGF-beta, and MIP-1 alpha both inhibit very primitive CD34+2)CD38- cells, but they are not equally potent. The effects of TGF-beta and MIP-1 alpha on more mature progenitor cells are more complex. Our results and data from the literature indicate that, as progenitor cells mature, they reach a "pivotal point" at a certain stage in their differentiation pathway, depending on the inhibitor, where they are no longer inhibited or where they may even be stimulated by the former inhibitor to proliferate.
authors.affiliation: Laboratory of Experimental Hematology, University of Antwerp (UIA/UZA), Belgium.
authors.forename: P C
authors.initials: PC
authors.lastname: Van Ranst
authors.forename: H W
authors.initials: HW
authors.lastname: Snoeck
authors.forename: F
authors.initials: F
authors.lastname: Lardon
authors.forename: M
authors.initials: M
authors.lastname: Lenjou
authors.forename: G
authors.initials: G
authors.lastname: Nijs
authors.forename: S F
authors.initials: SF
authors.lastname: Weekx
authors.forename: I
authors.initials: I
authors.lastname: Rodrigus
authors.forename: Z N
authors.initials: ZN
authors.lastname: Berneman
authors.forename: D R
authors.initials: DR
authors.lastname: Van Bockstaele
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000032:analysis*; D000943:Antigens, Differentiation / Q000032:analysis*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D054407:Chemokine CCL4; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1