Overlapping roles for granulocyte-macrophage colony-stimulating factor and interleukin-3 in eosinophil homeostasis and contact hypersensitivity

被引:30
作者
Gillessen, S
Mach, N
Small, C
Mihm, M
Dranoff, G
机构
[1] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[3] Univ Hosp Geneva, Dept Internal Med, Div Oncol, Geneva, Switzerland
[4] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA
关键词
D O I
10.1182/blood.V97.4.922
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Studies of mice rendered deficient in granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) have established unique roles for these cytokines in pulmonary homeostasis, resistance to infection, and antigen-specific T- and B-cell responses, In addition to these distinctive properties, however, GM-CSF and IL-3 also stimulate the development and activation of hematopoietic cells in many similar ways, raising the possibility that each factor might partially compensate for the other's absence in singly deficient mice. To test whether endogenous GM-CSF and IL-3 mediate redundant functions in vivo, we generated mice lacking both cytokines through sequential gene targeting experiments in embryonic stem (ES) cells. Surprisingly, doubly deficient animals, but not single knockouts, showed increased numbers of circulating eosinophils, Doubly deficient mice, moreover, developed weaker contact hypersensitivity reactions to haptens applied epicutaneously then mice deficient in either factor alone. Together, these findings delineate overlapping roles for GM-CSF and IL-3 in hematopoiesis and immunity. (C) 2001 by The American Society of Hematology.
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页码:922 / 928
页数:7
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