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
Kanakura, Y.; Sugahara, H.; Mitsui, H.; Ikeda, H.; Furitsu, T.; Yagura, H.; Kitayama, H.; Kanayama, Y.; Matsuzawa, Y.
Cancer Research 53(3): 675-680
1993
ISSN/ISBN: 0008-5472 PMID: 8425202 Document Number: 415951
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.