Induction of upmodulation of homing receptors in cloned hemopoietic progenitors by growth factors.
Recognition and selective seeding of hemopoietic cells to the marrow after intravenous transplantation is a function of membrane protein known as homing receptor (HR), which is a lectin with galactosyl and mannosyl specificities. We have previously shown that ex vivo incubation of marrow cells with IL-3 or GM-CSF enhances the seeding efficiency and that this enhancement may be the result of upmodulation of homing receptors. In the present work, we have shown that incubation of two cloned progenitor cell lines, FDCP-1 and FDCP-mix, with IL-3 or GM-CSF resulted in a dose-dependent increase in the number of HR per cell. Interferon-gamma did not have such an effect. The upmodulation of receptors was the result of enhanced de novo synthesis and transport of the protein as it was ablated by cyclohexamide, monensin or NH4Cl. On the other hand, degradation of the protein was not affected by the growth factors. The possible mechanisms whereby a brief exposure to growth factor ex vivo could lead to enhancement of homing efficiency are discussed. Induction of upmodulation of HR by ex vivo incubation of donor cells with certain hemopoietic growth factors, could be a useful strategy for enhancing marrow reconstitution after bone marrow transplantation. This could reduce the cost and prevent the side effects of in vivo growth factor therapy.
Shiota
Y
Y
Department of Veterans Affairs Medical, Jackson, MS 39216.
Minguell
J
J
Zanjani
E D
ED
Tavassoli
M
M
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D008985:Monensin / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D007377:Interleukin-3; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D000643:Ammonium Chloride; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008985:Monensin; D003513:Cycloheximide