Abstract:
:We investigated the in vivo effects of erythropoietin (EPO) on granulopoiesis and, conversely, the effect of granulocyte colony-stimulating factor (G-CSF) treatment on erythropoiesis. Recombinant human EPO at four different doses in combination with recombinant human G-CSF also at four different doses was simultaneously administered for 7 days to splenectomized mice. In total, 16 different combinations of growth factors were thus tested. G-CSF administration increased granulocyte production as expected, whereas immature colony-forming unit granulocyte-macrophage numbers were decreased. EPO analogously increased late erythroid cell numbers. Both EPO and G-CSF dose-dependently inhibited late cell stages of the opposite lineage, with EPO abrogating G-CSF-stimulated granulopoiesis and, conversely, G-CSF inhibiting EPO-stimulated erythropoiesis. In a subsequent experiment, we tested whether these lineage-competitive effects could be prevented by coadministering stem cell factor (SCF). In these three factor-treated mice, all granuloid and erythroid cell stages increased, thereby reducing the effect of the mutual inhibition. We conclude that EPO-stimulated erythropoiesis and G-CSF-stimulated granulopoiesis inhibited each other at a late level. Simultaneous SCF administration increased the input into both the erythroid and granuloid compartment and thereby compensated the mutual inhibition. This study shows that intricate dose-response relationships exist between various growth factors that should be carefully analyzed before combinations of these factors are used in humans.
journal_name
Bloodjournal_title
Bloodauthors
de Haan G,Engel C,Dontje B,Nijhof W,Loeffler Msubject
Has Abstractpub_date
1994-12-15 00:00:00pages
4157-63issue
12eissn
0006-4971issn
1528-0020journal_volume
84pub_type
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