A Distinct Pathway of Cell-Mediated Apoptosis Initiated by Granulysin
Author(s) -
Allan Kaspar,
Satoshi Okada,
Jayant Kumar,
Francis R. Poulain,
Katerina A. Drouvalakis,
Ameeta Kelekar,
Dennis A. Hanson,
Ruth M. Kluck,
Yasumichi Hitoshi,
Daniel E. Johnson,
Christopher J. Froelich,
Craig B. Thompson,
Donald D. Newmeyer,
Alberto Anel,
Carol Clayberger,
Alan M. Krensky
Publication year - 2001
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.167.1.350
Subject(s) - granulysin , granzyme , cytochrome c , ctl* , microbiology and biotechnology , apoptosis , granzyme b , programmed cell death , cytotoxic t cell , caspase , biology , mitochondrion , fas ligand , perforin , chemistry , biochemistry , in vitro
Granulysin is an antimicrobial and tumoricidal molecule expressed in granules of CTL and NK cells. In this study, we show that granulysin damages cell membranes based upon negative charge, disrupts the transmembrane potential (Deltapsi) in mitochondria, and causes release of cytochrome c. Granulysin-induced apoptosis is blocked in cells overexpressing Bcl-2. Despite the release of cytochrome c, procaspase 9 is not processed. Nevertheless, activation of caspase 3 is observed in granulysin-treated cells, suggesting that granulysin activates a novel pathway of CTL- and NK cell-mediated death distinct from granzyme- and death receptor-induced apoptosis.
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