Effect of recombinant interferons alpha and gamma on XXXX bone marrow-derived megakaryocytic progenitor cells.

@entity1 @entity3692
Interferons (IFNs) have been shown to suppress the proliferation of @entity1 pluripotent hematopoietic progenitor cells, CFU-GEMM, and committed erythroid (BFU-E, CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. However, no information is yet available concerning the effect of IFNs on @entity1 megakaryocytic progenitor cells CFU-Mk. Furthermore the mechanisms underlying the inhibitory activity of IFNs are still controversial. Therefore highly purified recombinant IFN preparations, rIFN-alpha and @entity3692 , were assessed for their influence on in vitro growth of @entity1 bone marrow-derived CFU-Mk as well as CFU-GEMM. In addition, the role of hematopoietic accessory cells, that is, adherent cells and T lymphocytes, in the mediation of the suppressive effect of rIFNs was examined. When added to unseparated bone marrow cells, both rIFN preparations significantly inhibited colony formation with 50% inhibition of CFU-Mk occurring at 22 U/mL for rIFN-alpha and 59 U/mL for @entity3692 , while 50% inhibition of CFU-GEMM occurred at 59 U/mL for rIFN-alpha and 101 U/mL for @entity3692 . The suppressive effect of rIFN-alpha and @entity3692 was selectively abolished by monoclonal antibodies (MoAbs) against rIFN-alpha and @entity3692 , thus confirming that the inhibitory activity was due to the rIFN preparations used. The antiproliferative effect of rIFN-alpha and @entity3692 on CFU-GEMM growth was not associated with a decrease in the percentage of mixed colonies containing megakaryocytic cells as assessed by use of the MoAb C17.28 against platelet glycoprotein IIIa. Removal of adherent cells and T lymphocytes from the target bone marrow cells had no influence on the suppressive effect of rIFN-alpha, whereas it significantly reduced the inhibitory effect of @entity3692 on the growth of megakaryocytic colonies and the other hematopoietic progenitors. The data indicate that (1) @entity1 megakaryocytopoiesis is markedly inhibited by rIFN-alpha and @entity3692 , and (2) the inhibitory effect of rIFN-alpha is due to a direct action on hematopoietic progenitor cells, whereas the effect of @entity3692 is mediated to a significant degree through accessory cell populations.
