Human interleukin-3 inhibits the binding of granulocyte-macrophage colony-stimulating factor and interleukin-5 to basophils and strongly enhances their functional activity.
The human T cell-derived cytokines interleukin (IL)-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5 were examined for their ability to bind specifically to human basophils and to regulate their function. Scatchard analysis of equilibrium binding studies showed that IL-3 and GM-CSF, bound to basophils with apparent dissociation constants (KD) = 8 x 10(-11) M and 3.9 x 10(-11) M, respectively. Specificity studies under conditions that prevent receptor internalization showed that the binding of IL-3, GM-CSF, and IL-5 was not inhibited by tumor necrosis factor (TNF)-alpha, IL-1 beta, interferon (IFN)-gamma, or G-CSF. However, receptors for IL-3, GM-CSF, and IL-5 interacted with each other on the basophil membrane, showing a unique spectrum of cross-reactivity, with IL-3 competing for GM-CSF and IL-5 binding, whereas GM-CSF and IL-5 showed little or no competition for IL-3 binding. In order to relate the binding properties of these cytokines to function, they were tested for their ability to influence basophil histamine release in an IgE/anti-IgE-dependent system. We found a hierarchy in the stimulation of basophil with the order of potency being IL-3 greater than GM-CSF greater than IL-5. In addition, IL-3 stimulated larger amounts of histamine release than GM-CSF or IL-5. The observation that IL-3 interacts with receptors for GM-CSF and IL-5 may have a bearing on its stronger functional effects and suggests a major role for IL-3 in the pathogenesis of hypersensitivity syndromes.
Department of Human Immunology, Institute of Medical and Veterinary Science, Adelaide, South Australia.
A F
AF
Lopez
J M
JM
Eglinton
A B
AB
Lyons
P M
PM
Tapley
L B
LB
To
L S
LS
Park
S C
SC
Clark
M A
MA
Vadas
D001491:Basophils / Q000378:metabolism* / Q000502:physiology; D001667:Binding, Competitive; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006636:Histamine Release / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000502:physiology*; D015848:Interleukin-5 / Q000378:metabolism*; D007457:Iodine Radioisotopes; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000378:metabolism
D007377:Interleukin-3; D015848:Interleukin-5; D007457:Iodine Radioisotopes; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016185:Receptors, Interleukin-3; D016178:Granulocyte-Macrophage Colony-Stimulating Factor