Modulation of bone marrow cell functions in vitro by bestatin (ubenimex).
Bestatin (ubenimex), the microbial leucil-aminopeptidase B inhibitor, has been shown previously to stimulate both interleukin-1 (IL-1) and IL-2 production and to enhance T-cell, as well as macrophage mediated immunoreaction when administered in vivo in mice. Here we show that although Bestatin has no direct growth stimulatory activity, it enhances the growth of GM-CFU populations in semisolide culture and stimulates the cell production in liquide organotypic Hematon cultures in synergy with recombinant human GM-CSF. In long term human bone marrow culture Bestatin accelerated the adipocytic differentiation among colony forming stroma cells (F-CFU). Our data provide further evidences that Bestatin may interact with the hemopoietic cell renewal system at different levels of biological organisation.
Blazsek
I
I
Service des Maladies Sanguines et Tumorales, Hôpital Paul-Brousse, Villejuif, France.
Comisso
M
M
Misset
J L
JL
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007930:Leucine; C012211:ubenimex