Reciprocal inhibition of binding between interleukin 3 and granulocyte-macrophage colony-stimulating factor to human eosinophils.
125I-labeled recombinant human interleukin 3 (IL-3) bound, at 4 degrees C, to a single class of high-affinity receptors on human eosinophils with an apparent dissociation constant (Kd) of 470 pM, but it did not bind to human neutrophils. 125I-labeled recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) also bound to a single class of high-affinity receptors on eosinophils with an apparent Kd of 44 pM and on neutrophils with an apparent Kd of 70 pM. These binding characteristics were consistent with the biological activities of IL-3 and GM-CSF on eosinophils and with the lack of stimulation of neutrophil function by IL-3. Specificity studies under conditions shown to prevent receptor internalization showed that the binding of 125I-labeled IL-3 to eosinophils was partially inhibited by GM-CSF but not by other cytokines. Reciprocal experiments with 125I-labeled GM-CSF showed that IL-3 but not other cytokines partially inhibited binding to eosinophils. In contrast, the binding of 125I-labeled GM-CSF to neutrophils was not inhibited by IL-3 or other cytokines tested. Quantitative inhibition binding experiments on eosinophils showed that the reciprocal inhibition between IL-3 and GM-CSF was not complete up to a concentration of heterologous ligand of 100 nM. These results show that (i) IL-3 binds to eosinophils but not neutrophils and (ii) IL-3 and GM-CSF specifically interact on the surface of eosinophils, providing a possible mechanism for the overlapping activities of IL-3 and GM-CSF on these cells.
Lopez
A F
AF
Division of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Eglinton
J M
JM
Gillis
D
D
Park
L S
LS
Clark
S
S
Vadas
M A
MA
D000920:Antibody-Dependent Cell Cytotoxicity; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism*; D007700:Kinetics; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor; D011971:Receptors, Immunologic / Q000378:metabolism*; D016185:Receptors, Interleukin-3; D011994:Recombinant Proteins / Q000378:metabolism
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007377:Interleukin-3; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D011971:Receptors, Immunologic; D016185:Receptors, Interleukin-3; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor