Document Detail

Effects of recombinant human granulocyte and macrophage colony-stimulating factors on signal transduction pathways in human granulocytes.
MedLine Citation:
PMID:  3119708     Owner:  NLM     Status:  MEDLINE    
We studied the ability of the recombinant human-active hemopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSFrh) and granulocyte colony-stimulating factor (G-CSFrh) to activate receptor-mediated transduction pathways which have been implicated in the stimulation of cytotoxic functions in granulocytes. With the use of a panel of fluorescent probes, we found that these two growth factors exerted no detectable immediate effect on the resting transmembrane electrical potential, the intracellular concentration of free calcium ions, or the cytosolic pH of isolated, mature granulocytes. However, when granulocytes were "primed" by preincubation for 90 min with GM-CSFrh or G-CSFrh, the rate of membrane depolarization induced by 10(-7) M N-formyl-methionyl-leucyl-phenylalanine, but not the rate of rise in free calcium ions, was greatly accelerated. In examining potential mechanisms to account for the priming effect of these growth factors, we found that although they did not induce translocation of protein kinase C or stimulate significant degranulation, they each directly caused prompt release of arachidonic acid from plasma membrane phospholipids. Our data indicate that although GM-CSFrh and G-CSFrh do not activate the transduction signals that have most clearly been implicated in receptor-mediated activation of cytotoxic functions in granulocytes--namely, those coupled to membrane depolarization or release of intracellular calcium ions--they appear directly to induce the release of arachidonic acid esterified to membrane phospholipids, an event which may represent the receptor-mediated activation of membrane phospholipases and which may contribute to the "priming" of the cells for enhancement of their functional responsiveness.
R Sullivan; J D Griffin; E R Simons; A I Schafer; T Meshulam; J P Fredette; A K Maas; A S Gadenne; J L Leavitt; D A Melnick
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  139     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1987 Nov 
Date Detail:
Created Date:  1987-12-22     Completed Date:  1987-12-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3422-30     Citation Subset:  AIM; IM    
Department of Medicine, University Hospital, Boston, MA 02118.
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MeSH Terms
Arachidonic Acid
Arachidonic Acids / biosynthesis
Calcium / metabolism
Colony-Stimulating Factors / pharmacology*
Cytosol / analysis
Granulocytes / drug effects*,  physiology
Hydrogen-Ion Concentration
Membrane Lipids / metabolism
Membrane Potentials / drug effects
N-Formylmethionine Leucyl-Phenylalanine / pharmacology
Phospholipases / metabolism
Phospholipids / metabolism
Recombinant Proteins / pharmacology
Grant Support
Reg. No./Substance:
0/Arachidonic Acids; 0/Colony-Stimulating Factors; 0/Membrane Lipids; 0/Phospholipids; 0/Recombinant Proteins; 506-32-1/Arachidonic Acid; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; 7440-70-2/Calcium; EC 3.1.-/Phospholipases

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