Fas/Apo-1 (CD95)-mediated apoptosis of neutrophils with Fas ligand (CD95L)-expressing tumors is crucial for induction of inflammation by neutrophilic polymorphonuclear leukocytes associated with antitumor immunity

被引:15
|
作者
Shimizu, M
Fontana, A
Takeda, Y
Yoshimoto, T
Tsubura, A
Matsuzawa, A
机构
[1] Kansai Med Univ, Dept Pathol, Moriguchi, Osaka 5708506, Japan
[2] Tokyo Metropolitan Univ, Intractable Dis Res Ctr, Shinjuku Ku, Tokyo 1608402, Japan
[3] Univ Tokyo, Inst Med Sci, Lab Anim Res Ctr, Minato Ku, Tokyo 1068639, Japan
[4] Univ Tokyo, Inst Med Sci, Dept Surg, Minato Ku, Tokyo 1068639, Japan
[5] Univ Zurich Hosp, Dept Internal Med, CH-8044 Zurich, Switzerland
[6] Tokyo Metropolitan Org Med Res, Tokyo Metropolitan Inst Med Sci, Dept Mol Oncol, Bunkyo Ku, Tokyo 1138613, Japan
关键词
apoptosis; Fas; CD95; Fas ligand; CD95L; neutrophils; infiltration; chemotaxis; inflammation; tumor immunity; hepatoma MH134;
D O I
10.1006/cimm.2000.1734
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To address how Fast-expressing tumors induce neutrophil emigration and abrogate tumorigenicity, we investigated the behavior of FasLcDNA-transfected hepatoma MH134 (G2) cells injected into wild-type (+) mice, lpr(cg)/lpr(cg) (lpr(cg)) mice with death domain (DD)mutated Fas, and gld/gld lpr/lpr (gld/lpr) mice with defects in FasL/Fas, G2 cells were eradicated after extensive infiltration of neutrophils around them in + mice but formed tumors without such infiltration in lpr(cg) and gld/lpr mice, Abundant cell debris suggestive of apoptosis of infiltrating neutrophils was found among G2 tumor cells in + mice but a few neutrophils infiltrating among G2 cells were intact in lpr(cg) and gld/lpr mice. Collectively, these results indicate the crucial role of Fas DD in Fas-mediated apoptosis of neutrophils and suggest that apoptosis of neutrophils with Fast-expressing tumors may trigger the extensive infiltration of neutrophils, resulting in violent inflammation and ultimately in the eradication of tumor cells. (C) 2001 Academic Press.
引用
收藏
页码:41 / 48
页数:8
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