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Effect of granulocyte-macrophage colony-stimulating factor and
interleukin-3 on interleukin-8 production by human neutrophils and
monocytes
GW Takahashi, DF Andrews , MB Lilly, JW Singer and MR Alderson
Bone Marrow Transplant Program, Seattle Veterans Affairs Medical Center, WA
98108.
Interleukin-8 (IL-8) is a major neutrophil chemoattractant and functional
stimulant that is induced by IL-1, tumor necrosis factor alpha (TNF alpha),
and lipopolysaccharide (LPS). We report that recombinant human (rh)
granulocyte-macrophage colony-stimulating factor (GM-CSF) and rhIL-3 are
also potent inducers of IL-8 messenger RNA (mRNA) accumulation and protein
secretion by normal peripheral blood monocytes. Neutrophils produce IL-8 in
response to GM-CSF but not to IL- 3. In contrast, recombinant human
granulocyte-CSF (rhG-CSF), at concentrations as high as 100 ng/mL, does not
induce IL-8 in either cell type. rhGM-CSF also induces IL-8 mRNA expression
and IL-8 protein in the promonocytic cell line, U-937, whereas rhG-CSF does
not. IL-8 secretion by monocytes was stimulated within 2 hours after
incubation with rhGM-CSF or rhIL-3. Stimulation of neutrophils with
rhGM-CSF resulted in an increase in cell-associated IL-8 at 4 hours. At 24
hours, cell-associated IL-8 levels declined, whereas secreted IL-8 levels
increased. In contrast, virtually all IL-8 induced in monocytes appeared as
secreted protein. Neither rhGM-CSF nor rhIL-3 induced detectable secretion
of IL-1, TNF alpha, or IL-6 protein by monocytes. rhGM-CSF, and to a lesser
degree rhIL-3, potently stimulated IL-8 secretion in cultures of
heparinized whole blood, whereas rhG-CSF had no significant effect on IL-8
secretion. Induction of IL-8 by GM-CSF may be physiologically important in
enhancing the acute inflammatory response.
Volume 81,
Issue 2,
pp. 357-364,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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