A distinct pathway of cell-mediated apoptosis initiated by granulysin
AA Kaspar, S Okada, J Kumar, FR Poulain, KA Drouvalakis, A Kelekar, DA Hanson, RM Kluck, Y Hitoshi, DE Johnson, CJ Froelich, CB Thompson, DD Newmeyer, A Anel, C Clayberger, AM Krensky
Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2001
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.
Awarded by NIAID NIH HHS
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES