Abstract |
Tissue transglutaminase (TGase2) is a protein-crosslinking enzyme known to be associated with the in vivo apoptosis program. Here we report that apoptosis could be induced in TGase2-/- mice; however, the clearance of apoptotic cells was defective during the involution of thymus elicited by dexamethasone, anti-CD3 antibody, or gamma-irradiation, and in the liver after induced hyperplasia. The lack of TGase2 prevented the production of active transforming growth factor-beta1 in macrophages exposed to apoptotic cells, which is required for the up-regulation of TGase2 in the thymus in vivo, for accelerating deletion of CD4+CD8+ cells and for efficient phagocytosis of apoptotic bodies. The deficiency is associated with the development of splenomegaly, autoantibodies, and immune complex glomerulonephritis in TGase2-/- mice. These findings have broad implications not only for diseases linked to inflammation and autoimmunity but also for understanding the interrelationship between the apoptosis and phagocytosis process.
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Authors | Zsuzsa Szondy, Zsolt Sarang, Peter Molnar, Tamas Nemeth, Mauro Piacentini, Pier Giorgio Mastroberardino, Laura Falasca, Daniel Aeschlimann, Judit Kovacs, Ildiko Kiss, Eva Szegezdi, Gabriella Lakos, Eva Rajnavolgyi, Paul J Birckbichler, Gerry Melino, Laszlo Fesus |
Journal | Proceedings of the National Academy of Sciences of the United States of America
(Proc Natl Acad Sci U S A)
Vol. 100
Issue 13
Pg. 7812-7
(Jun 24 2003)
ISSN: 0027-8424 [Print] United States |
PMID | 12810961
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Autoantibodies
- Immunoglobulin M
- Tgfb1 protein, mouse
- Transforming Growth Factor beta
- Transforming Growth Factor beta1
- Protein Glutamine gamma Glutamyltransferase 2
- Transglutaminases
- GTP-Binding Proteins
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Topics |
- Animals
- Apoptosis
- Autoantibodies
(metabolism)
- Blotting, Western
- CD4-Positive T-Lymphocytes
(metabolism)
- CD8-Positive T-Lymphocytes
(metabolism)
- GTP-Binding Proteins
(genetics, physiology)
- Hepatocytes
(metabolism)
- Immunoglobulin M
(metabolism)
- Listeria monocytogenes
(metabolism)
- Macrophages
(metabolism)
- Mice
- Microscopy, Electron
- Phagocytosis
- Polymerase Chain Reaction
- Protein Glutamine gamma Glutamyltransferase 2
- Saccharomyces cerevisiae
(metabolism)
- Thymus Gland
(metabolism, pathology, ultrastructure)
- Transforming Growth Factor beta
(metabolism)
- Transforming Growth Factor beta1
- Transglutaminases
(genetics, physiology)
- Up-Regulation
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