IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor potentiate basophil mediator release stimulated by eosinophil granule major basic protein.
We have examined the potential of IL-3, IL-5, and granulocyte-macrophage (GM)-CSF to enhance basophil activation by eosinophil granule major basic protein (MBP). Preincubating basophil-containing mononuclear cells with 0.01 to 10 ng/ml IL-3 or IL-5 for 15 min at 37 degrees C caused a concentration-dependent enhancement of histamine release stimulated by 1.5 microM MBP. Statistically significant enhancement was evident at 1 ng/ml and was maximal at 10 ng/ml. Preincubation with GM-CSF similarly enhanced MBP-induced histamine release. A 10- to 15-min preincubation with IL-5 maximally increased the level of MBP-stimulated histamine release. Preincubation of cells with 10 ng/ml IL-3 or IL-5 reduced the MBP concentrations required for histamine release by three- to fourfold and enhanced the rate of MBP-induced histamine release. MBP-stimulated histamine release before or after cytokine priming was independent of cytotoxicity as measured by 51Cr release. Consistent with a direct action of the cytokines on basophils, flow cytometric analysis demonstrated the presence of IL-3 and GM-CSF receptors on basophils. MBP also stimulated low levels of leukotriene C4 (LTC4) release from basophils of 84 to 99% purity, and experiments using enriched (18-63%) basophil preparations demonstrated that preincubation with IL-3, IL-5, and GM-CSF also potentiated MBP-stimulated leukotriene C4 release up to threefold in parallel with histamine release. These results indicate that IL-3, IL-5, and GM-CSF may contribute to the pathogenesis of allergic and other disorders characterized by eosinophilia in part through potentiation of basophil mediator release stimulated by MBP.
Sarmiento
E U
EU
Department of Immunology/Microbiology, Rush Medical College, Chicago, IL 60612, USA.
Espiritu
B R
BR
Gleich
G J
GJ
Thomas
L L
LL
D001491:Basophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D001798:Blood Proteins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D047091:Eosinophil Granule Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000096:biosynthesis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D018123:Receptors, Interleukin / Q000032:analysis; D016185:Receptors, Interleukin-3 / Q000032:analysis; D053649:Receptors, Interleukin-5; D012260:Ribonucleases
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D007377:Interleukin-3; D015848:Interleukin-5; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D016185:Receptors, Interleukin-3; D053649:Receptors, Interleukin-5; D017997:Leukotriene C4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D012260:Ribonucleases