Cell surface tissue transglutaminase is involved in adhesion and migrationof monocytic cells on fibronectin

Expression of tissue transglutaminase (transglutaminase II, tTG) was shown to increase drastically during monocyte differentiation into macrophages; h owever, its role in monocytic cells remains largely unknown. This study des cribes a novel function of cell surface tTG as an adhesion and migration re ceptor for fibronectin (Fn). Two structurally related transglutaminases, tT G and the A subunit of factor XIII (FXIIIA), are expressed on the surface o f monocytic cells, whereas only surface tTG is associated with multiple Int egrins of the beta (1) and beta (3) subfamilies. Both surface levels of tTG and the amounts of integrin-bound tTG are sharply up-regulated during the conversion of monocytes into macrophages. In contrast, a reduction in biosy nthesis and surface expression of FXIIIA accompanies monocyte differentiati on. Cell surface tTG is colocalized with beta (1)- and beta (3)-integrins i n podosomelike adhesive structures of macrophages adherent on Fn. Down-regu lation of surface tTG by expression of antisense tTG construct or its inhib ition by function-blocking antibodies significantly decreases adhesion and spreading of monocytic cells on Fn and, in particular, on the gelatin-bindi ng fragment of Fn consisting of modules I6II1,2I7-9. Likewise, interfering with the adhesive function of surface tTG markedly reduces migration of mye loid cells on Fn and its gelatin-binding fragment. These data demonstrate t hat cell surface tTG serves as an integrin-associated adhesion receptor tha t might be involved in extravasation and migration of monocytic cells into tissues containing Fn matrices during inflammation. (C) 2001 by The America n Society of Hematology.