HUMAN INTERLEUKIN-3 INHIBITS THE BINDING OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR AND INTERLEUKIN-5 TO BASOPHILS AND STRONGLY ENHANCES THEIR FUNCTIONAL-ACTIVITY

被引:123
作者
LOPEZ, AF
EGLINTON, JM
LYONS, AB
TAPLEY, PM
TO, LB
PARK, LS
CLARK, SC
VADAS, MA
机构
[1] INST MED & VET SCI, DEPT HAEMATOL, ADELAIDE, SA 5000, AUSTRALIA
[2] IMMUNEX CORP, SEATTLE, WA 98101 USA
[3] GENET INST, CAMBRIDGE, MA 02140 USA
关键词
D O I
10.1002/jcp.1041450111
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The human T cell‐derived cytokines interleukin (IL)‐3, granulocyte‐macrophage colony‐stimulating factor (CM‐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 × 10−11M and 3.9 × 10−11M, 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)‐α, IL‐1β, interferon (IFN)‐γ, 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 >GM‐CSF >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. Copyright © 1990 Wiley‐Liss, Inc.
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页码:69 / 77
页数:9
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