Development of multipotential haemopoietic stem cells to neutrophils is associated with increased expression of receptors for granulocyte macrophage colony-stimulating factor: altered biological responses to GM-CSF during development.
Authors
Heyworth, Clare MHampson, J
Dexter, T Michael
Walker, F
Burgess, A W
Kan, O
Cook, N
Vallance, S J
Whetton, Anthony D
Affiliation
Cancer Research Campaign Department of Experimental Haematology, Paterson Institute for Cancer Research, Withington, Manchester, UK.Issue Date
1991
Metadata
Show full item recordAbstract
Interleukin-3 (IL-3) dependent multipotent haemopoietic stem cells FDCP-Mix A4 (A4) were induced to differentiate and develop into mature neutrophils in response to Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) plus granulocyte CSF (G-CSF). This resulted in an increase in cell number over seven days of culture, following which the cells lost the ability to undergo further proliferation. The effect of GM-CSF on these cells has been assessed at various stages of development. Clonogenic cells, able to respond to GM-CSF, were generated only at days 3, 4 post-induction. From day 5 onwards, mature post-mitotic neutrophils are produced and clonogenic cells are lost. Loss of proliferative potential, in response to GM-CSF, was confirmed using [3H]-thymidine incorporation. Receptors for GM-CSF, were also measured during development using [125I]-GM-CSF binding assays. Although the dissociation constant for GM-CSF binding sites did not vary considerably, the number of such sites increased dramatically from about 20 (day 0, when the cells have a primitive morphology) to about 1000 by day 6 (when the cells are predominantly mature neutrophils). GM-CSF-stimulated Na+/H+ antiport activation was also determined. Although few GM-CSF receptors are expressed at day 0, there is a significant response (63% of maximal) to GM-CSF in terms of intracellular alkalinisation: this response increased markedly until, by day 4 (700 GM-CSF binding sites/cell), there is a maximal activation of the antiport by GM-CSF. By day 7 (greater than 900 GM-CSF binding sites/cell), however, there is significant reduction in activation of the Na+/H+ antiport by GM-CSF. Nonetheless, increased viability of these mature cells is still seen in response to GM-CSF. These results suggest that not only does expression of GM-CSF receptors alter during development of multipotential cells to mature neutrophils, but that these receptors are coupled to different intracellular effector mechanisms as the cells progressively mature.Citation
Development of multipotential haemopoietic stem cells to neutrophils is associated with increased expression of receptors for granulocyte macrophage colony-stimulating factor: altered biological responses to GM-CSF during development. 1991, 5 (2):87-98 Growth FactorsJournal
Growth FactorsDOI
10.3109/08977199109000274PubMed ID
1837466Type
ArticleLanguage
enISSN
0897-7194ae974a485f413a2113503eed53cd6c53
10.3109/08977199109000274
Scopus Count
Collections
Related articles
- Granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor, PIXY-321, stem cell factor, interleukin-3, and interleukin-7: receptor binding and effects on clonogenic proliferation in acute lymphoblastic leukemia.
- Authors: Drach D, Estrov Z, Zhao S, Drach J, Cork A, Collins D, Kantarjian H, Andreeff M
- Issue date: 1994 Dec
- Neutrophils activated by granulocyte-macrophage colony-stimulating factor express receptors for interleukin-3 which mediate class II expression.
- Authors: Smith WB, Guida L, Sun Q, Korpelainen EI, van den Heuvel C, Gillis D, Hawrylowicz CM, Vadas MA, Lopez AF
- Issue date: 1995 Nov 15
- Impact of benzene metabolites on differentiation of bone marrow progenitor cells.
- Authors: Irons RD, Stillman WS
- Issue date: 1996 Dec
- Stimulation of human hematopoietic progenitor cell proliferation and differentiation by recombinant human interleukin 3. Comparison and interactions with recombinant human granulocyte-macrophage and granulocyte colony-stimulating factors.
- Authors: Ottmann OG, Abboud M, Welte K, Souza LM, Pelus LM
- Issue date: 1989 Feb
- Stimulation of granulopoiesis by transforming growth factor beta: synergy with granulocyte/macrophage-colony-stimulating factor.
- Authors: Keller JR, Jacobsen SE, Sill KT, Ellingsworth LR, Ruscetti FW
- Issue date: 1991 Aug 15