Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor

被引:122
作者
Ishii, S
Nagase, T
Tashiro, F
Ikuta, K
Sato, S
Waga, I
Kume, K
Miyazaki, J
Shimizu, T
机构
[1] UNIV TOKYO,FAC MED,DEPT BIOCHEM,BUNKYO KU,TOKYO 113,JAPAN
[2] UNIV TOKYO,FAC MED,DEPT GERIATR,BUNKYO KU,TOKYO 113,JAPAN
[3] UNIV TOKYO,FAC MED,DEPT DIS RELATED GENE REGULAT RES SANDOZ,BUNKYO KU,TOKYO 113,JAPAN
[4] JAPAN TOBACCO INC,LIFE SCI RES LAB,AOBA KU,YOKOHAMA,KANAGAWA 227,JAPAN
关键词
beta-actin promoter; hyperplasia; lipopolysaccharide; melanocytic tumor; methacholine;
D O I
10.1093/emboj/16.1.133
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although platelet-activating factor (PAF) has been shown to exert pleiotropic effects on isolated cells or tissues, controversy still exists as to whether it plays significant pathophysiological roles in vivo. To answer this question, we established transgenic mice overexpressing a guinea-pig PAF receptor (PAFR). The transgenic mice showed a bronchial hyperreactivity to methacholine and an increased mortality when exposed to bacterial endotoxin. An aberrant melanogenesis and proliferative abnormalities in the skin were also observed in the transgenic mice, some of which spontaneously bore melanocytic tumors in the dermis after aging. Thus, PAFR transgenic mice proved to be a useful model for studying the basic pathophysiology of bronchial asthma and endotoxin-induced death, and screening of therapeutics for these disorders. Furthermore, our findings provide new insights regarding the role of PAF in the morphogenesis of dermal tissues as well as the mitogenic activity of PAF and PAFR in vivo.
引用
收藏
页码:133 / 142
页数:10
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