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
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
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
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