Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo

被引：333

作者：

Pham, CTN

Ley, TJ ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Div Rheumatol, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Div Bone Marrow Transplantat, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Div Stem Cell Biol, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA

[5] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 1999年 / 96卷 / 15期

关键词：

D O I：

10.1073/pnas.96.15.8627

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that has been implicated in the processing of granzymes, which are neutral serine proteases exclusively expressed in the granules of activated cytotoxic lymphocytes. In this report, we show that cytotoxic lymphocytes derived from DPPI-/- mice contain normal amounts of granzymes A and B, but these molecules retain their prodipeptide domains and are inactive. Cytotoxic assays with DPPI-/- effector cells reveal severe defects in the induction of target cell apoptosis (as measured by [I-125] UdR release) at both early and late time points; this defect is comparable to that detected in perforin-/- or granzyme A-/- x B-/- cytotoxic lymphocytes. DPPI therefore plays an essential role in the in vivo processing and activation of granzymes A and B, which are required for cytotoxic lymphocyte granule-mediated apoptosis.

引用

页码：8627 / 8632

页数：6

共 44 条

[1] Augmented inflammatory responses and altered wound healing in cathepsin G-deficient mice [J].