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Differential activation of leukotriene biosynthesis by granulocyte-
macrophage colony-stimulating factor and interleukin-5 in an eosinophilic
substrain of HL-60 cells
KA Scoggan, AW Ford-Hutchinson and DW Nicholson
Merck Frosst Centre for Therapeutic Research, Pointe Claire-Dorval,
Montreal, Quebec, Canada.
Cytokines can stimulate eosinophils to produce cysteinyl leukotrienes (LTs)
in the lung that provoke tissue destruction associated with asthma. Priming
of an eosinophilic substrain of HL-60 cells (HL-60#7) with recombinant
human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) before
ionophore challenge was found to produce an apparent 45% increase in total
LT production in a dose-dependent manner (ED50 = 150 pmol/L) that could be
accounted for by a decrease in the time required for maximal formation of
LTs. GM-CSF had no effect on the kinetic parameters of LTC4 synthase and
therefore probably acts upstream of this catalytic event. Incubation with
interleukin-5 (IL-5), however, had no effect on LT biosynthesis. This
differential priming ability was not a consequence of different receptor
populations or differences in the affinity or stability of the
ligand-receptor complexes of GM-CSF and IL-5. GM-CSF and IL-5 each
displayed similar populations of high-affinity binding sites and neither
GM-CSF nor IL-5 were able to cross-compete for the other's receptor binding
sites. Analysis of phosphotyrosine patterns suggest that IL-5 is incapable
of transducing a signal in eosinophilic HL-60#7 cells even though IL-5 and
GM-CSF receptors mediate signal transduction via a common beta-chain
component that is also necessary for high-affinity binding. Overall, this
unique system may permit the dissection of distinct events responsible for
specific intracellular signals transduced separately by GM-CSF or IL-5.
Volume 86,
Issue 9,
pp. 3507-3516,
11/01/1995
Copyright © 1995 by The American Society of Hematology
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