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Papers In Press, published online ahead of print February 25, 2004
Division of Immunogenetics, University of Göttingen, Göttingen 37073
Corresponding Author: rdresse{at}gwdg.de
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 granzyme B 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 a Mpr300 or Mpr46-dependent pathway of granzyme-mediated killing and provide new insight in the internalization of monomeric and complexed granzyme B
J. Biol. Chem, 10.1074/jbc.M313108200
Submitted on December 2, 2003
Revised on February 25, 2004
Accepted on February 25, 2004
Granzyme-mediated cytotoxicity does not involve the mannose 6-phosphate receptors on target cells
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