Enhanced proliferative activity of PIXY-321, the granulocyte-macrophage colony-stimulating factor and interleukin-3 fusion protein.
Previous studies with the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) fusion protein, PIXY-321, demonstrated the enhanced biological activity of this molecule in comparison with GM-CSF or IL-3 alone or in combination. Here, we performed experiments to determine the proliferative effect of PIXY-321 on 13 constitutively growth factor-dependent human leukemia cell lines in comparison with GM-CSF, IL-3 and their combination using as read-out parameters the 48-hour 3H-thymidine incorporation assay and viable cell counts after in vitro culture for 7-8 days. Whereas one cell line was not responsive to any of these three cytokines, the other 12 cell lines showed variable degrees of growth in response to these effector molecules. PIXY-321 increased proliferation as measured by thymidine uptake relative to IL-3, GM-CSF or GM-CSF + IL-3 by 34% (range 5-448%), 12% (range 0-122%), and 6% (range 1-13%), respectively. PIXY-321 induced a mean increase of 32%, 30% and 11% in cell counts relative to the values obtained with IL-3, GM-CSF or GM-CSF + IL-3, respectively. Altogether, these data indicate that PIXY-321 stimulates proliferation of immature hematopoietic cells substantially better than equivalent concentrations of the single growth factors GM-CSF and IL-3. This hybrid growth factor showed a marginal to modest, but definite and reproducible increase in proliferation compared to the combination of GM-CSF plus IL-3. In summary, the fusion cytokine protein PIXY-321 appears to have biological effects superior to those elicited by its components, singly or in combination. This unique molecule should represent a useful tool in studies on the mechanisms underlying cytokine ligand-receptor interaction and the subsequent signal transduction. The use of PIXY-321 provides an opportunity for taking greater advantage in vitro and in vivo of the hematopoietic stimulatory activities of GM-CSF and IL-3.
Drexler
H G
HG
DSMZ-German Collection of Microorganisms & Cell Cultures, Department of Human and Animal Cell Cultures Braunschweig, Germany. hdr@gbf-braunschweig.de
Meyer
C
C
D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007377:Interleukin-3; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor