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

Z. Szondy, Z. Sarang, P. Molnár, Tamás Németh, Mauro Piacentini, Pier Giorgio Mastroberardino, Laura Falasca, Daniel Aeschlimann, Judit Kovács, Ildikó Kiss, Eva Szegezdi, Gabriella Lakos, E. Rajnavolgyi, Paul J. Birckbichler, Gerry Melino, L. Fésüs

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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 γ-irradiation, and in the liver after induced hyperplasia. The lack of TGase2 prevented the production of active transforming growth factor-β1 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.

Original languageEnglish
Pages (from-to)7812-7817
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number13
DOIs
Publication statusPublished - Jun 24 2003

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Phagocytosis
Macrophages
Apoptosis
Thymus Gland
Cytophagocytosis
Splenomegaly
Transforming Growth Factors
Glomerulonephritis
Antigen-Antibody Complex
Autoimmunity
Autoantibodies
Dexamethasone
Hyperplasia
Anti-Idiotypic Antibodies
Up-Regulation
Inflammation
Liver
Enzymes
transglutaminase 2
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells. / Szondy, Z.; Sarang, Z.; Molnár, P.; Németh, Tamás; Piacentini, Mauro; Mastroberardino, Pier Giorgio; Falasca, Laura; Aeschlimann, Daniel; Kovács, Judit; Kiss, Ildikó; Szegezdi, Eva; Lakos, Gabriella; Rajnavolgyi, E.; Birckbichler, Paul J.; Melino, Gerry; Fésüs, L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 13, 24.06.2003, p. 7812-7817.

Research output: Contribution to journalArticle

Szondy, Z, Sarang, Z, Molnár, P, Németh, T, Piacentini, M, Mastroberardino, PG, Falasca, L, Aeschlimann, D, Kovács, J, Kiss, I, Szegezdi, E, Lakos, G, Rajnavolgyi, E, Birckbichler, PJ, Melino, G & Fésüs, L 2003, 'Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 13, pp. 7812-7817. https://doi.org/10.1073/pnas.0832466100
Szondy, Z. ; Sarang, Z. ; Molnár, P. ; Németh, Tamás ; Piacentini, Mauro ; Mastroberardino, Pier Giorgio ; Falasca, Laura ; Aeschlimann, Daniel ; Kovács, Judit ; Kiss, Ildikó ; Szegezdi, Eva ; Lakos, Gabriella ; Rajnavolgyi, E. ; Birckbichler, Paul J. ; Melino, Gerry ; Fésüs, L. / Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 13. pp. 7812-7817.
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