Linked Life Data

8251409

Source:http://linkedlifedata.com/resource/pubmed/id/8251409

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-1-11
pubmed:abstractText
The GM-CSF receptor (GM-CSFR) is composed of alpha and beta subunits. Surface expression of the alpha chain alone leads to low affinity GM-CSF binding and of both subunits to high affinity binding; the beta chain is required for transducing a proliferative signal. Studies of GM-CSFR expression have concentrated largely on static events occurring under conditions of binding equilibrium. We have examined the dynamic regulation of high and low affinity GM-CSFR expression in neutrophils (1100 +/- 200 R/cell, KD 50 +/- 15 pM) and a GM-CSF dependent human leukaemic cell line, TF-1 (2000 +/- 450 R/cell KD 15 +/- 5 pM) and 8600 +/- 1150 R/cell KD 1.8 +/- 0.3 nM). The addition of GM-CSF to TF-1 cells (350 pM, 4 h at 37 degrees C) caused a reduction in subsequent binding of 125I-GM-CSF at low ligand concentration (100 pM) (following a low pH wash to remove surface bound ligand) to 16 +/- 4% and a reduction in binding at high ligand concentration (2 nM 125I-GM-CSF) to 36 +/- 9% of control. Scatchard analysis showed complete down-regulation of high affinity GM-CSFR and a significant reduction in low affinity GM-CSFR. In neutrophils, concentration-response curves of ligand induced receptor down-regulation at 37 degrees C showed that observed down-modulation was more than 10-fold greater than predicted by static equilibrium binding data and correlated closely with GM-CSF priming of the neutrophil respiratory burst. The addition of IL-3 to TF-1 cells at 37 degrees C reduced 100 pM 125I-GM-CSF binding to 18 +/- 4% and 2 nM 125I-GM-CSF binding to 46 +/- 5% of control. TF-1 cells, but not neutrophils, were able to re-express GM-CSFR following removal of GM-CSF from medium. TF-1 proliferation assays showed that pulsed GM-CSF (0.35-3.5 nM) for up to 4 h did not cause a significant increase in 3H-thymidine incorporation which required the continued presence of GM-CSF (control 2875 +/- 208 cpm, pulsed GM-CSF 5 ng/ml 4972 +/- 1344, continuous GM-CSF 5 ng/ml 17249 +/- 2982). Therefore, proliferation of TF-1 cells required the continued presence of GM-CSF at a time when there was no detectable surface high affinity GM-CSFR.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0007-1048
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
42-9
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Dynamic modulation of the cell surface expression of the granulocyte-macrophage colony-stimulating factor receptor.
pubmed:affiliation
Department of Haematology, University College London Medical School.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't