Transglutaminase 2 is needed for the formation of an efficient phagocyte portal in macrophages engulfing apoptotic cells

Beáta Tóth, Éva Garabuczi, Zsolt Sarang, György Vereb, György Vámosi, Daniel Aeschlimann, Bernadett Blaskó, Bálint Bécsi, Ferenc Erdõdi, Adam Lacy-Hulbert, Ailiang Zhang, Laura Falasca, Raymond B. Birge, Zoltán Balajthy, Gerry Melino, László Fésüs, Zsuzsa Szondy

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Abstract

Transglutaminase 2 (TG2), a protein cross-linking enzyme with many additional biological functions, acts as coreceptor for integrin β3. We have previously shown that TG2-/- mice develop an age-dependent autoimmunity due to defective in vivo clearance of apoptotic cells. Here we report that TG2 on the cell surface and in guanine nucleotide-bound form promotes phagocytosis. Besides being a binding partner for integrin β3, a receptor known to mediate the uptake of apoptotic cells via activating Rac1, we also show that TG2 binds MFG-E8 (milk fat globulin EGF factor 8), a protein known to bridge integrin β3 to apoptotic cells. Finally, we report that in wild-type macrophages one or two engulfing portals are formed during phagocytosis of apoptotic cells that are characterized by accumulation of integrin β3 and Rac1. In the absence of TG2, integrin β3 cannot properly recognize the apoptotic cells, is not accumulated in the phagocytic cup, and its signaling is impaired. As a result, the formation of the engulfing portals, as well as the portals formed, is much less efficient. We propose that TG2 has a novel function to stabilize efficient phagocytic portals.

Original languageEnglish
Pages (from-to)2084-2092
Number of pages9
JournalJournal of Immunology
Volume182
Issue number4
DOIs
Publication statusPublished - Feb 15 2009

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ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Tóth, B., Garabuczi, É., Sarang, Z., Vereb, G., Vámosi, G., Aeschlimann, D., Blaskó, B., Bécsi, B., Erdõdi, F., Lacy-Hulbert, A., Zhang, A., Falasca, L., Birge, R. B., Balajthy, Z., Melino, G., Fésüs, L., & Szondy, Z. (2009). Transglutaminase 2 is needed for the formation of an efficient phagocyte portal in macrophages engulfing apoptotic cells. Journal of Immunology, 182(4), 2084-2092. https://doi.org/10.4049/jimmunol.0803444