In vitro- and ex vivo-derived cytolytic leukocytes from granzyme A x B double knockout mice are defective in granule-mediated apoptosis but not lysis of target cells

Details

Ressource 1Download: BIB_FB52EEE20228.P001.pdf (146.27 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_FB52EEE20228
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In vitro- and ex vivo-derived cytolytic leukocytes from granzyme A x B double knockout mice are defective in granule-mediated apoptosis but not lysis of target cells
Journal
Journal of Experimental Medicine
Author(s)
Simon  M. M., Hausmann  M., Tran  T., Ebnet  K., Tschopp  J., ThaHla  R., Mullbacher  A.
ISSN
0022-1007 (Print)
Publication state
Published
Issued date
11/1997
Volume
186
Number
10
Pages
1781-6
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Nov 17
Abstract
Granzyme (gzm) A and gzmB have been implicated in Fas-independent nucleolytic and cytolytic processes exerted by cytotoxic T (Tc) cells, but the underlying mechanism(s) remains unclear. In this study, we compare the potential of Tc and natural killer (NK) cells of mice deficient in both gzmA and B (gzmAxB-/-) with those from single knockout mice deficient in gzmA (-/-), gzmB (-/-), or perforin (-/-) to induce nuclear damage and lysis in target cells. With the exception of perforin-/-, all in vitro- and ex vivo-derived Tc and NK cell populations from the mutant strains induced 51Cr-release in target cells at levels and with kinetics similar to those of normal mice. This contrasts with their capacity to induce apoptotic nuclear damage in target cells. In gzmAxB-/- mice, Tc/NK-mediated target cell DNA fragmentation was not observed, even after extended incubation periods (10 h), but was normal in gzmA-deficient and only impaired in gzmB-deficient mice in short-term (2-4 h), but not long-term (4-10 h), nucleolytic assays. This suggests that gzmA and B are critical for Tc/NK granule- mediated nucleolysis, with gzmB being the main contributor, while target cell lysis is due solely to perforin and independent of both proteases.
Keywords
Animals Apoptosis/*immunology Cytoplasmic Granules/*enzymology/immunology Cytotoxicity Tests, Immunologic *Cytotoxicity, Immunologic DNA Fragmentation Female Granzymes Leukemia L1210 Lymphoma Male Mast-Cell Sarcoma Membrane Glycoproteins/physiology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Pore Forming Cytotoxic Proteins Serine Endopeptidases/*deficiency/genetics/physiology T-Lymphocytes, Cytotoxic/*enzymology/immunology/metabolism Tumor Cells, Cultured
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 15:18
Last modification date
20/08/2019 16:26
Usage data