Susceptibility of monocytes to lymphokine-activated killer cell lysis:
effect of granulocyte-macrophage colony-stimulating factor and
interleukin-3
JY Djeu, R Widen and DK Blanchard
Department of Medical Microbiology and Immunology, University of South
Florida College of Medicine, Tampa 33612.
Cultured human monocytes have been shown to be susceptible to lysis by
autologous lymphokine-activated killer (LAK) cells. To determine factors
that might modulate the sensitivity of monocytes to lysis, we cultured
adherent peripheral blood leukocytes (PBL) in the presence of
granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3
(IL-3) since these cytokines have been reported to affect both functional
and physical characteristics of monocytes. Both recombinant human GM-CSF
and IL-3 were found to significantly enhance the susceptibility of
monocytes to lysis by LAK cells in a dose- dependent manner, with GM-CSF
being slightly more effective. In a kinetics study, the lysability of
monocytes increased after two days of incubation with either cytokine, with
maximal susceptibility occurring after four to six days of culture. The
effects of GM-CSF and IL-3 appeared to be specific for monocytes since
culture of either nonadherent cells or granulocytes, which are normally
resistant to LAK- mediated lysis, did not induce sensitivity. While the
effects of GM-CSF and IL-3 have been shown to be synergistic in some cases,
they did not act synergistically to induce monocyte susceptibility to LAK
lysis. In cold target experiments cytokine-treated monocytes reciprocally
blocked lysis, suggesting that similar target structures were modulated
with either factor. FACS analysis and sodium dodecyl sulfate polyacrylamide
gel electrophoresis (SDS-PAGE) demonstrated comparable modulation of
surface antigens with either GM-CSF or IL-3. Thus, these cytokines can
serve to augment susceptibility of monocytes to LAK cells, emphasizing the
complex interactions that occur in the immune system.
Volume 73,
Issue 5,
pp. 1264-1271,
04/01/1989
Copyright © 1989 by The American Society of Hematology