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Title
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TGF- and MIP-1 exert their main inhibitory activity on very primitive cells but show opposite effects on more mature human hematopoietic progenitors
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Author
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Abstract
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| 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(++)CD38(-) 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(++)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. |
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Language
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English
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Source (journal)
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Experimental hematology. - Oak Ridge, Tenn., 1973, currens
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Publication
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Oak Ridge, Tenn.
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1996
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ISSN
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0301-472X
1873-2399
[online]
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Volume/pages
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24
:13
(1996)
, p. 1509-1515
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ISI
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A1996VW26000008
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