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The effect of three human recombinant hematopoietic growth factors
(granulocyte-macrophage colony-stimulating factor, granulocyte colony-
stimulating factor, and interleukin-3) on phagocyte oxidative activity
GW Sullivan, HT Carper and GL Mandell
Department of Medicine, University of Virginia, Charlottesville 22908.
Hematopoietic growth factors not only modulate blood progenitor cell
activity but also alter the function of mature phagocytes. Recombinant
human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 1 ng/mL
for 60 min) did not stimulate luminol-enhanced chemiluminescence of
polymorphonuclear leukocytes (PMNs) in suspension but primed PMN for as
much as a 15-fold increase in chemiluminescence in response to f-met-
leu-phe (fMLP). Mixed mononuclear leukocytes (monocytes [approximately 20%]
and lymphocytes [approximately 80%]; MNL) chemiluminescence was very low
even after rhGM-CSF priming, but MNLs added to the PMNs (PMN- MNL) resulted
in near doubling of rhGM-CSF-primed PMN fMLP-stimulated chemiluminescence.
The enhancing factor(s) from MNLs were inherent rather than induced by the
GM-CSF, and purified lymphocytes increased GM-CSF-primed PMN
chemiluminescence equal to mixed MNLs. We could not detect cell-free
"enhancing factor(s)," but cell-to-cell contact further enhanced
rhGM-CSF-primed fMLP-stimulated PMN-MNL oxidative activity by 40%.
Polyclonal rabbit anti-tumor necrosis factor (TNF) (but not preimmune
serum) decreased both fMLP-stimulated rhGM-CSF- primed PMNs and PMN-MNL
chemiluminescence, suggesting that TNF on the PMN surface is enhancing
GM-CSF-primed chemiluminescence. GM-CSF priming markedly increased PMN
superoxide release (sevenfold), but PMN superoxide release was not further
enhanced by the presence of MNLs. Recombinant human granulocyte
colony-stimulating factor (rhG-CSF) and interleukin-3 (rhIL-3) displayed
much smaller effects on pure PMNs and mixed PMN-MNL chemiluminescence and
superoxide release than rhGM-CSF. rhGM-CSF primes PMNs for increased
oxidative activity more than rhG-CSF and rhIL-3. Maximal oxidative activity
was observed when mixed PMN-MNL were primed with GM-CSF in a cell
pellet-promoting cell-to-cell contact. This enhanced activity can be
attributed, in part, to both inherent enhancing factor(s) on lymphocytes
and PMN-associated TNF induced by GM-CSF.
Volume 81,
Issue 7,
pp. 1863-1870,
04/01/1993
Copyright © 1993 by The American Society of Hematology

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