Over-expression of integrin β3 can partially overcome the defect of integrin β3 signaling in transglutaminase 2 null macrophages

Transglutaminase 2 (TG2) is a protein crosslinking enzyme with many additional biological functions. We have previously shown that in TG2^-/- mice the in vivo clearance of apoptotic cells is defective leading to autoimmunity. TG2 contributes to the formation of phagocytic portals by binding to both integrin β₃, a known phagocytic receptor, and its bridging molecule, MFG-E8. In TG2 null macrophages integrin β₃ cannot accumulate around the apoptotic cells and its signaling is impaired. In the present study we describe a subline of TG2 null mice, in which a compensatory increase in integrin β₃ expression, which resulted alone in a high receptor concentration around the apoptotic cells without the requirement for accumulation, partially corrected the defect in integrin β₃ signaling. Our data provide a proof for the concept that the function of TG2 is to stabilize accumulated integrin β₃ concentration in the phagocytic cup.