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

• Published in: Proceedings of the National Academy of Sciences - PNAS 2003-06, Vol.100 (13), p.7812-7817
• Main Authors: Szondy, Z, Sarang, Z, Molnar, P, Nemeth, T, Piacentini, M, Mastroberardino, P G, Falasca, L, Aeschlimann, D, Kovacs, J, Kiss, I, Szegezdi, E, Lakos, G, Rajnavoelgyi, E, Birckbichler, P J, Melino, G, Fesues, L
• Format: Article
• Language: English
• ISSN: 0027-8424
• DOI: 10.1073/pnas.0832466100

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 super(-/-) 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- beta 1 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 super(-/-) 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.