TY - JOUR
T1 - Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells
AU - Szondy, Zsuzsa
AU - Sarang, Zsolt
AU - Molnár, Péter
AU - Németh, Tamás
AU - Piacentini, Mauro
AU - Mastroberardino, Pier Giorgio
AU - Falasca, Laura
AU - Aeschlimann, Daniel
AU - Kovács, Judit
AU - Kiss, Ildikó
AU - Szegezdi, Eva
AU - Lakos, Gabriella
AU - Rajnavölgyi, Eva
AU - Birckbichler, Paul J.
AU - Melino, Gerry
AU - Fésüs, László
PY - 2003/6/24
Y1 - 2003/6/24
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0832466100
DO - 10.1073/pnas.0832466100
M3 - Article
C2 - 12810961
AN - SCOPUS:0038271789
VL - 100
SP - 7812
EP - 7817
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 13
ER -