A distinct pathway of cell-mediated apoptosis initiated by granulysin.
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.
Kaspar
A A
AA
Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Okada
S
S
Kumar
J
J
Poulain
F R
FR
Drouvalakis
K A
KA
Kelekar
A
A
Hanson
D A
DA
Kluck
R M
RM
Hitoshi
Y
Y
Johnson
D E
DE
Froelich
C J
CJ
Thompson
C B
CB
Newmeyer
D D
DD
Anel
A
A
Clayberger
C
C
Krensky
A M
AM
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D003574:Cytochrome c Group / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D008563:Membrane Lipids / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D003574:Cytochrome c Group; C075005:GNLY protein, human; D008563:Membrane Lipids