Over-expression of integrin b3 can partially overcome the defect of integrin b3 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 super(-) super(/) super(-) 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 b sub(3), a known phagocytic receptor, and its bridging molecule, MFG-E8. In TG2 null macrophages integrin b sub(3) 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 b sub(3) expression, which resulted alone in a high receptor concentration around the apoptotic cells without the requirement for accumulation, partially corrected the defect in integrin b sub(3) signaling. Our data provide a proof for the concept that the function of TG2 is to stabilize accumulated integrin b sub(3) concentration in the phagocytic cup.