The distinct developmental routes of dendritic cells and mast cells from murine bone marrow cultures with interleukin-3 are unclear. We found that short-term bone marrow cultures with interleukin-3 after 8-10 d consist of about 10%-30% dendritic cells and 70%-90% mast cell precursors, and only after 4-6 wk do homogeneous populations of mast cells emerge. Phenotypical and functional analysis of interleukin-3/dendritic cells revealed a high similarity with myeloid dendritic cells generated with granulocyte-macrophage colony stimulating factor in the expression of myeloid dendritic cell markers (CD11c+ B220- CD8alpha- CD11b+), major histocompatibility complex II and costimulatory molecules, endocytosis, maturation potential, interleukin-12 production, and T cell priming. Interleukin-3/dendritic cells expressed higher levels of interleukin-3 receptor, however. To dissect the interleukin-3/dendritic cell and mast cell development, we sorted fresh bone marrow cells into six subsets by the antibodies ER-MP12 (CD31) and ER-MP20 (Ly-6C). Both interelukin-3/dendritic cells and granulocyte-macrophage colony stimulating factor/dendritic cells develop from the same bone marrow populations, including the ER-MP12neg, ER-MP20high bone marrow monocytes. In contrast, mast cells only developed from ER-MP12(int+high), ER-MP20neg bone marrow cell subsets, indicating that different precursors exist for interleukin-3/dendritic cells and mast cells. Established mast cell cultures could not be converted to dendritic cells or stimulated to express major histocompatibility complex II molecules in vitro or home to lymph node T cell areas in vivo. In summary, we show that dendritic cells generated from bone marrow precursors with interleukin-3 are clearly myeloid and develop via a different pathway compared to bone marrow mast cells.

Anticancer research

Recombinant human interleukin-3 opposes the effects of vitamins A and D on HL-60 human myeloid leukaemia cells.

Article

Author: Maurer, H R ; Spandidos, D A ; Hassan, H T ; Tsiriyotis, C

Interleukin-3 (IL-3), retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (calcitriol) (vitamin D) have achieved objective responses in phase I/II clinical trials in myeloid leukaemia and preleukaemia patients. In an effort to explore any additive or synergistic interactions between these biological agents which could provide the basis for improved therapeutic regimens for myeloid leukaemia patients, we have investigated the effects of IL-3 on both RA- and vitamin D-induced actions in HL-60 human myeloid leukaemia cells, which have receptors for these three agents, in both clonogenic microassays and liquid suspension cultures. The proliferative stimulus of IL-3 overrode and reversed the antiproliferative actions of both RA and vitamin D, the latter being more sensitive to the counter-acting effect of IL-3. Whereas only high concentrations of IL-3: 1000 or more U/ml were able to oppose the antiproliferative effect of RA, all concentrations of IL-3 including the low concentration of 10 U/ml, significantly counteracted the anti-proliferative action of vitamin D. RA restrained the proliferative stimulus of IL-3 partly at low physiological concentrations and almost completely at high pharmacological concentrations. The same results were reproduced in liquid suspension culture. Whereas RA restrained the proliferative stimulus of IL-3, vitamin D failed to restrain it. However, IL-3 did not induce differentiation or affect RA- or vitamin D-induced differentiation of HL-60 cells. The present results suggest that the clinical use of the combination of low concentration of IL-3 with RA and not with vitamin D might restrain the progression of myeloid leukaemia incurred during the treatment with IL-3 in some preleukaemic patients.

100 Deals associated with Interleukin-3 (Cangene Corp.)

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Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Phase 3	-	Cangene Corp.	-
Leukemia	Phase 3	-	Cangene Corp.	-

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