PMID- 7608562
OWN - NLM
STAT- MEDLINE
DCOM- 19950816
LR  - 20071115
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 155
IP  - 2
DP  - 1995 Jul 15
TI  - IL-4 promotes macrophage development by rapidly stimulating lineage restriction 
      of bipotent granulocyte-macrophage colony-forming cells.
PG  - 845-53
AB  - Granulocyte macrophage colony-forming cells (GM-CFC) are bipotential progenitor 
      cells that can proliferate and develop into macrophages in response to macrophage 
      CSF or into neutrophils in response to stem cell factor or granulocyte CSF. These 
      cytokines promoted growth and development in highly enriched GM-CFC. In 
      [3H]thymidine suicide assays, IL-4 was shown to stimulate proliferation of GM-CFC 
      to the same degree as IL-3 and other potent mitogens for GM-CFC. IL-4 also 
      maintained the clonogenic potential of enriched GM-CFC over a 2-day period. 
      However, after several days in the presence of IL-4, the GM-CFC began to die and 
      retained blast cell morphology characteristic of the isolated GM-CFC. When a high 
      concentration of IL-4 was added to GM-CFC with neutrophilic stimuli, the response 
      of these cells was altered because macrophages were formed. This effect was 
      achieved by a 4-h preincubation with IL-4, suggesting that an early signal 
      produced by IL-4 promotes lineage restriction, although IL-4 itself cannot 
      promote development. IL-4, like macrophage CSF, translocates PKC-alpha to the 
      nucleus in GM-CFC, this redistribution of protein kinase C alpha (PKC-alpha) 
      being inhibited by calphostin C (a PKC inhibitor). Calphostin C also blocked 
      IL-4-mediated development of macrophages in stem cell factor- and 
      granulocyte-CSF-treated cells. This is further evidence that PKC-alpha 
      translocation is involved in the commitment of GM-CFC to macrophage development. 
      This data also suggests that agonist-stimulated lineage commitment can be 
      uncoupled from development in normal hematopoietic cells.
FAU - Nicholls, S E
AU  - Nicholls SE
AD  - Department of Biochemistry and Applied Molecular Biology, UMIST, Manchester, 
      United Kingdom.
FAU - Heyworth, C M
AU  - Heyworth CM
FAU - Dexter, T M
AU  - Dexter TM
FAU - Lord, J M
AU  - Lord JM
FAU - Johnson, G D
AU  - Johnson GD
FAU - Whetton, A D
AU  - Whetton AD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 207137-56-2 (Interleukin-4)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Cell Differentiation/drug effects
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Granulocytes/*cytology
MH  - Hematopoietic Stem Cells/*drug effects
MH  - Interleukin-4/*pharmacology
MH  - Macrophages/*cytology/*drug effects
MH  - Mice
MH  - Protein Kinase C/antagonists & inhibitors/drug effects/genetics
MH  - Signal Transduction/drug effects
MH  - Stem Cells/drug effects
MH  - Translocation, Genetic/drug effects
EDAT- 1995/07/15 00:00
MHDA- 1995/07/15 00:01
CRDT- 1995/07/15 00:00
PHST- 1995/07/15 00:00 [pubmed]
PHST- 1995/07/15 00:01 [medline]
PHST- 1995/07/15 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1995 Jul 15;155(2):845-53.