Susceptibility of monocytes to lymphokine-activated killer cell lysis: effect of granulocyte-macrophage colony-stimulating factor and interleukin-3.
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.
Djeu
J Y
JY
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa 33612.
Widen
R
R
Blanchard
D K
DK
D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2; D007377:Interleukin-3 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000032:analysis; D009000:Monocytes / Q000032:analysis / Q000145:classification / Q000276:immunology*; D010641:Phenotype
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007376:Interleukin-2; D007377:Interleukin-3; D008565:Membrane Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor