title: The role of tissue transglutaminase (transglutaminase type II) for the intestinal manifestations of murine semi-allogenic graft-versus-host disease.
abstract: The intestinal manifestation of acute murine semi-allogenic graft-versus-host (GvH) disease is characterized by the occurrence of lymphocytic infiltrates in the lamina propria, by crypt hyperplasia and villous atrophy. In a histological respect, this animal model resembles human celiac disease. Tissue transglutaminase (tTG) (transglutaminase type II) has been identified to be the major B cell autoantigen in celiac disease. Furthermore, tissue transglutaminase has been implicated to be involved in its pathogenesis. Therefore, we aimed to investigate whether tissue transglutaminase is expressed in the intestines of GvH animals and whether its inhibition has any effect on the intestinal histology. Sera of patients with celiac disease and anti-tTG antibodies were purified. These antibodies were used for immuno-histochemistry of jejunal cryosection from GvH and syngenic control animals at day 6 after lymphocyte transfer. Furthermore, GvH mice were treated with antitTG antibodies and with the inhibitor of tissue transglutaminase monodansyl-cadaverine. The effect of this treatment on the development of crypt hyperplasia and villous atrophy were examined by light microscopy of hematoxylin-eosin (H&E) stained jejunal paraffin sections. We found a strong subepithelial expression of tissue transglutaminase in GvH animals but not in syngenic control mice. The localization of tTG seemed to be associated with the extracellular matrix (ECM). However, neither the treatment of GvH animals with anti-tTG antibodies nor the application of mono-dansyl-cadaverine prevented the development of crypt hyperplasia and villous atrophy. Similar to the situation in human celiac disease tissue, transglutaminase is highly expressed in the intestine of animals undergoing a semi-allogenic graft-versus-host reaction. However, this enzyme is probably not involved in the development of crypt hyperplasia and villous atrophy in this animal model.
authors.affiliation: I. Medizinische Universitätsklinik, Schittenhelmstrasse 12, 24105 Kiel, Germany. estueber@1med.uni-kiel.de
authors.forename: Eckhard
authors.initials: E
authors.lastname: Stüber
authors.forename: Rainer
authors.initials: R
authors.lastname: Noth
authors.forename: Maren
authors.initials: M
authors.lastname: Dirks
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
authors.forename: Ullrich
authors.initials: U
authors.lastname: Fölsch
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use; D002103:Cadaverine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D017710:Lymphocyte Transfusion / Q000379:methods; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*
chemical_list: D000906:Antibodies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; C008542:monodansylcadaverine; D002103:Cadaverine