Journal article

Cytosolic delivery of granzyme B by bacterial toxins: Evidence that endosomal disruption, in addition to transmembrane pore formation, is an important function of perforin

KA Browne, E Blink, VR Sutton, CJ Froelich, DA Jans, JA Trapani

Molecular and Cellular Biology | AMER SOC MICROBIOLOGY | Published : 1999

Abstract

Granule-mediated cell killing by cytotoxic lymphocytes requires the combined actions of a membranolytic protein, perforin, and granule-associated granzymes, but the mechanism by which they jointly kill cells is poorly understood. We have tested a series of membrane-disruptive agents including bacterial pore-forming toxins and hemolytic complement for their ability to replace perforin in facilitating granzyme B-mediated cell death. As with perforin, low concentrations of streptolysin O and pneumolysin (causing 4,000 U/ml were perforin pores demonstrably large enough to account for transmembrane diffusion of granzyme B. We conclude that pore formation may allow granzyme B direct cytosolic acce..

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