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Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells.

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.
AuthorsZsuzsa 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
JournalProceedings 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
PMID12810961 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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