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Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2003 Jun 24; Vol. 100 (13), pp. 7812-7. Date of Electronic Publication: 2003 Jun 16. - Publication Year :
- 2003
-
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.
- Subjects :
- Animals
Autoantibodies metabolism
Blotting, Western
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes metabolism
Hepatocytes metabolism
Immunoglobulin M metabolism
Listeria monocytogenes metabolism
Mice
Microscopy, Electron
Polymerase Chain Reaction
Protein Glutamine gamma Glutamyltransferase 2
Saccharomyces cerevisiae metabolism
Thymus Gland metabolism
Thymus Gland pathology
Thymus Gland ultrastructure
Transforming Growth Factor beta metabolism
Transforming Growth Factor beta1
Up-Regulation
Apoptosis
GTP-Binding Proteins genetics
GTP-Binding Proteins physiology
Macrophages metabolism
Phagocytosis
Transglutaminases genetics
Transglutaminases physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 100
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 12810961
- Full Text :
- https://doi.org/10.1073/pnas.0832466100