Reduced mast cell and basophil numbers and function in Cpa3-Cre; Mcl-1fl/fl mice

被引：162

作者：

Lilla, Jennifer N. ^{[1
]}

Chen, Ching-Cheng ^{[1
,2
]}

Mukai, Kaori ^{[1
]}

BenBarak, Maya J. ^{[1
]}

Franco, Christopher B. ^{[1
]}

Kalesnikoff, Janet ^{[1
]}

Yu, Mang ^{[1
]}

Tsai, Mindy ^{[1
]}

Piliponsky, Adrian M. ^{[1
,3
]}

Galli, Stephen J. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA

[2] City Hope Natl Med Ctr, Div Stem Cell & Leukemia Res, Duarte, CA 91010 USA

[3] Seattle Childrens Res Inst, Ctr Immun & Immunotherapies, Seattle, WA USA

来源：

BLOOD | 2011年 / 118卷 / 26期

基金：

美国国家卫生研究院;

关键词：

CARBOXYPEPTIDASE-A; T-CELLS; DEFICIENT; SURVIVAL; MCL-1; DIFFERENTIATION; INFLAMMATION; MOUSE; RECRUITMENT; NEUTROPHILS;

D O I：

10.1182/blood-2011-03-343962

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

It has been reported that the intracellular antiapoptotic factor myeloid cell leukemia sequence 1 (Mcl-1) is required for mast cell survival in vitro, and that genetic manipulation of Mcl-1 can be used to delete individual hematopoietic cell populations in vivo. In the present study, we report the generation of C57BL/6 mice in which Cre recombinase is expressed under the control of a segment of the carboxypeptidase A3 (Cpa3) promoter. C57BL/6-Cpa3-Cre; Mcl-1(fl/fl) mice are severely deficient in mast cells (92%-100% reduced in various tissues analyzed) and also have a marked deficiency in basophils (58%-78% reduced in the compartments analyzed), whereas the numbers of other hematopoietic cell populations exhibit little or no changes. Moreover, Cpa3-Cre; Mcl-1(fl/fl) mice exhibited marked reductions in the tissue swelling and leukocyte infiltration that are associated with both mast cell-and IgE-dependent passive cutaneous anaphylaxis (except at sites en-grafted with in vitro-derived mast cells) and a basophil-and IgE-dependent model of chronic allergic inflammation, and do not develop IgE-dependent passive systemic anaphylaxis. Our findings support the conclusion that Mcl-1 is required for normal mast cell and basophil development/survival in vivo in mice, and also suggest that Cpa3-Cre; Mcl-1(fl/fl) mice may be useful in analyzing the roles of mast cells and basophils in health and disease. (Blood. 2011;118(26):6930-6938)

引用

页码：6930 / 6938

页数：9

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