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Title: Killing by cytotoxic T cells and natural killer cells: multiple granule serine proteases as initiators of DNA fragmentation.
Austin Authors: Trapani, Joseph A;Smyth, Mark J
Affiliation: Cellular Cytotoxicity Laboratory, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Jun-1993
Publication information: Immunology and Cell Biology; 71 ( Pt 3)(): 201-8
Abstract: The vectorial secretion of the contents of highly specialized cytoplasmic granules is of pivotal importance to the killing by cytotoxic T cells and natural killer cells. The purification and biochemical characterization of some of the granule constituents, in particular the pore-forming protein perforin, had engendered the notion that the killing of cellular targets was largely an osmotic phenomenon analogous to the insult delivered by complement attack. However, the apparent absence of membrane perforation in various examples of lymphocyte-mediated killing, and the observation that perforin alone could not account for apoptosis associated with programmed cell death, suggested that perforin activity represented, at best, only a part of the whole mechanism. More recently, the characterization of a large family of granule serine proteases (granzymes) has provided evidence that these molecules may collaborate in the killing process by inducing a 'suicide' pathway in target cells, resulting in DNA fragmentation. However, the serine proteases are inactive alone, their natural substrates have not been defined and they require access into the target cell cytoplasm via perforin-induced pores to exert their deleterious effects. Thus, we propose that the cytotoxic granule-mediated mechanism comprises at least two interdependent arms, perforin and serine proteases, that together are capable of inflicting cell death by osmotic shock and/or nuclear collapse.
Gov't Doc #: 8349302
DOI: 10.1038/icb.1993.22
Type: Journal Article
Subjects: Animals
Chondroitin Sulfate Proteoglycans.physiology
Cytoplasmic Granules.enzymology
Cytotoxicity, Immunologic
DNA Damage
Killer Cells, Natural.enzymology.immunology
Membrane Glycoproteins.physiology
Models, Biological
Pore Forming Cytotoxic Proteins
Sequence Homology, Amino Acid
Serine Endopeptidases.chemistry.genetics.physiology
T-Lymphocytes, Cytotoxic.enzymology.immunology
Appears in Collections:Journal articles

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