Functional expression of interleukin 2 receptor in a human factor-dependent megakaryoblastic leukemia cell line: evidence that granulocyte-macrophage colony-stimulating factor inhibits interleukin 2 binding to its receptor

Cancer Res. 1993 Feb 1;53(3):675-80.

Abstract

Human interleukin 2 (IL-2) is a member of the class of crucial regulators of lymphocyte proliferation. The action of IL-2 is known to be mediated through binding to a specific IL-2 receptor (IL-2R) which comprises at least two distinct proteins: IL-2R alpha (p55) and IL-2R beta (p70-75). However, the expression and function of IL-2R are largely unknown in acute myeloblastic leukemia cells. In a human granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or stem cell factor-dependent myeloid leukemia cell line (M07E), IL-2 was found to stimulate proliferation in a dose-dependent manner and to augment GM-CSF- and stem cell factor-induced proliferation of M07E cells. The expression of IL-2R beta on M07E cells was detectable with 125I-IL-2 binding and affinity cross-linking analyses and with a monoclonal antibody against IL-2R beta, Mik-beta 1. Although the expression of IL-2R beta was not down-regulated but somewhat up-regulated by treatment with GM-CSF in both mRNA and protein levels, GM-CSF was found to compete (75%) with radiolabeled IL-2 for binding to IL-2R on M07E cells, whereas no competition of GM-CSF binding was observed with IL-2 even at a 400-fold molar excess. These results suggest that IL-2R may be functionally expressed in some cases of acute myeloblastic leukemia cells and raise the possibility that IL-2 may have some effects on human myelopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Cell Division / drug effects
  • Cross-Linking Reagents / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Interleukin-2 / antagonists & inhibitors
  • Interleukin-2 / metabolism*
  • Interleukin-2 / pharmacology
  • Iodine Radioisotopes
  • Kinetics
  • Leukemia, Megakaryoblastic, Acute / genetics
  • Leukemia, Megakaryoblastic, Acute / metabolism
  • Leukemia, Megakaryoblastic, Acute / pathology*
  • RNA, Messenger / genetics
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Interleukin-2 / physiology*
  • Sensitivity and Specificity
  • Transcription, Genetic / genetics
  • Tumor Cells, Cultured

Substances

  • Cross-Linking Reagents
  • Interleukin-2
  • Iodine Radioisotopes
  • RNA, Messenger
  • Receptors, Interleukin-2
  • Granulocyte-Macrophage Colony-Stimulating Factor