title: Cell surface tissue transglutaminase is involved in adhesion and migration of monocytic cells on fibronectin.
abstract: Expression of tissue transglutaminase (transglutaminase II, tTG) was shown to increase drastically during monocyte differentiation into macrophages; however, its role in monocytic cells remains largely unknown. This study describes a novel function of cell surface tTG as an adhesion and migration receptor for fibronectin (Fn). Two structurally related transglutaminases, tTG and the A subunit of factor XIII (FXIIIA), are expressed on the surface of monocytic cells, whereas only surface tTG is associated with multiple integrins of the beta1 and beta3 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 biosynthesis and surface expression of FXIIIA accompanies monocyte differentiation. Cell surface tTG is colocalized with beta1- and beta3-integrins in podosomelike adhesive structures of macrophages adherent on Fn. Down-regulation of surface tTG by expression of antisense tTG construct or its inhibition by function-blocking antibodies significantly decreases adhesion and spreading of monocytic cells on Fn and, in particular, on the gelatin-binding fragment of Fn consisting of modules I6II1,2I7-9. Likewise, interfering with the adhesive function of surface tTG markedly reduces migration of myeloid cells on Fn and its gelatin-binding fragment. These data demonstrate that cell surface tTG serves as an integrin-associated adhesion receptor that might be involved in extravasation and migration of monocytic cells into tissues containing Fn matrices during inflammation.
authors.affiliation: Department of Biochemistry, The Holland Laboratory, American Red Cross, Rockville, MD 20855, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Akimov
authors.forename: A M
authors.initials: AM
authors.lastname: Belkin
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D022081:Cell Surface Extensions / Q000502:physiology; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004790:Enzyme Induction; D005353:Fibronectins / Q000378:metabolism*; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000201:enzymology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D011503:Transglutaminases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D018076:DNA, Complementary; D005353:Fibronectins; D019012:Integrin beta1; D039661:Integrin beta3; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C094990:adhesion receptor; D016173:Macrophage Colony-Stimulating Factor; D005780:Gelatin; D011503:Transglutaminases; D013755:Tetradecanoylphorbol Acetate