Enhancement of neutrophil function by granulocyte-macrophage colony-
stimulating factor involves recruitment of a less responsive subpopulation
MP Fletcher and JC Gasson
Department of Medicine, University of California, Davis, School of Medicine
95616.
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances
numerous functions of mature neutrophils (PMN) including phagocytosis,
superoxide responses to chemotaxins, antibody-dependent cellular
cytotoxicity, and expression of complement receptors. A central question
concerns whether the mechanism of enhancement involves quantitative
increases in the response of all cells v subpopulation recruitment. The
effects of GM-CSF on individual cell light scatter changes, membrane
potential, and oxidant responses induced by the chemoattractant
N-formyl-methionyl-leucyl-phenylalanine (FMLP) were assessed by flow
cytometry and by scoring individual cells for nitroblue tetrazolium dye
(NBT) reduction. GM-CSF produced a dose- and time-dependent shift in
forward light scatter that was very similar in character to that seen with
FMLP or leukotriene B4 stimulation. Although not capable of depolarizing
the cells directly, GM-CSF primed PMNs for enhanced membrane potential
responses to FMLP by significantly increasing the proportion of
depolarizing cells when compared with diluent-treated controls after a
60-minute incubation at 37 degrees C (79.4% +/- 3.4% v 29.5% +/- 4.7%
GM-CSF v diluent, mean +/- SE, P less than .005, n = 11). Subpopulation
recruitment by GM-CSF treatment was also demonstrated by the FMLP-elicited
NBT test. Taken together, these results indicate that GM-CSF can modulate
the function of mature PMN by enhancing the proportion of responsive cells.
Volume 71,
Issue 3,
pp. 652-658,
03/01/1988
Copyright © 1988 by The American Society of Hematology
