Granzyme-mediated cytotoxicity does not involve the mannose 6-phosphate receptors on target cells

被引:41
作者
Dressel, R
Raja, SM
Höning, S
Seidler, T
Froelich, CJ
von Figura, K
Günther, E
机构
[1] Univ Gottingen, Div Immunogenet, D-37073 Gottingen, Germany
[2] Northwestern Univ, Feinberg Sch Med, Evanston Healthcare Res Inst, Evanston, IL 60201 USA
[3] Univ Gottingen, Div Biochem 2, D-37073 Gottingen, Germany
[4] Univ Gottingen, Div Cardiol & Pneumol, D-37075 Gottingen, Germany
关键词
D O I
10.1074/jbc.M313108200
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
Cytotoxic T lymphocytes (CTL) and natural killer cells secrete granzymes to kill infected or transformed cells. The mannose 6-phosphate receptor (Mpr) 300 on target cells has been reported to function as receptor for secreted granzyme B. Using lymphoblasts and mouse embryonal fibroblast lines from Mpr300 and Mpr46 knockout mice, we show here that both receptors are not essential for CTL-induced apoptosis. Similarly, cells exposed to either monomeric granzyme B or granzyme B-serglycin complexes readily internalize the granzyme and undergo apoptosis in the absence of Mpr300 and Mpr46. Further, no colocalization of granzyme B and Mpr300 could be observed in target cells after internalization. In conclusion, these results strongly argue against an Mpr300- or Mpr46-dependent pathway of granzyme-mediated killing and provide new insight in the internalization of monomeric and complexed granzyme B.
引用
收藏
页码:20200 / 20210
页数:11
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