Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes

Details

Serval ID
serval:BIB_5BCF42C3E4D4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes
Journal
Journal of Experimental Medicine
Author(s)
Peters  P. J., Borst  J., Oorschot  V., Fukuda  M., Krahenbuhl  O., Tschopp  J., Slot  J. W., Geuze  H. J.
ISSN
0022-1007 (Print)
Publication state
Published
Issued date
05/1991
Volume
173
Number
5
Pages
1099-109
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May 1
Abstract
Cytotoxic T lymphocytes (CTL) contain granules that are exocytosed during specific interaction with target cells (TC). In this process, the granule contents, including the lethal protein perforin, as well as granzymes, a family of serine esterases, are delivered to the TC. Information regarding the routing of these proteins towards the granule and their exact localization within the granule is of primary importance to resolve the mechanism of granule-mediated TC killing. In this study, the subcellular localization of perforin, granzymes, and known endosomal and lysosomal marker proteins was determined in human and murine CTL, by immunogold labeling of ultrathin cryosections followed by electron microscopy. Perforin and granzymes can be detected in rough endoplasmic reticulum, Golgi complex, trans-Golgi reticulum, and in all cytotoxic granules. Within the granules, they have a similar distribution and are localized not only in the so-called dense core but also over the region containing small internal vesicles. This finding implies that perforin and granzymes can be released in membrane-enveloped and/or -associated form into the intercellular cleft formed upon CTL-TC interaction. On the basis of the present evidence, additional release of these molecules in soluble form cannot be excluded. The lysosomal membrane glycoproteins lamp-1, lamp-2, and CD63, are abundantly present on the granule-delimiting outer membrane, which becomes incorporated into the CTL plasma membrane during lethal hit delivery. In contrast, the cation-dependent mannose 6-phosphate receptor, known to be present in endosomes and absent from lysosomes, is found only in a minority of the granules. Together with our previous findings that the granules are acidic and connected to the endocytic pathway, these observations define CTL granules as secretory lysosomes.
Keywords
Animals Cell Line Cell Membrane/metabolism/ultrastructure Cytoplasmic Granules/metabolism/ultrastructure Endocytosis/physiology Endoplasmic Reticulum/metabolism/ultrastructure Golgi Apparatus/metabolism/ultrastructure Granzymes Humans Immunohistochemistry Lysosomes/*metabolism/physiology/ultrastructure Male Membrane Glycoproteins/metabolism Membrane Proteins/*metabolism Microscopy, Electron Pore Forming Cytotoxic Proteins Serine Endopeptidases/*metabolism T-Lymphocytes, Cytotoxic/cytology/metabolism/*ultrastructure
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:18
Last modification date
20/08/2019 15:14
Usage data