[Expression of adhesion molecules in hepatic graft-versus-host disease].
I investigated effects of spleen cells on hepatic graft-versus-host disease (GVHD) and expression of adhesion molecules in a murine bone marrow transplant model, since these cells contain abundant T cells and induce severe GVHD. Furthermore, I investigated effects of tumor necrosis factor alpha (TNF alpha) on liver damage and expression of adhesion molecules in a murine bone marrow transplant model. By injection of spleen cells, the dotty, partially focal T cell infiltration with necrosis of hepatocytes was found in the liver parenchyma. Expression of leukocyte function associated antigen-1 (LFA-1) and cluster of differentiation-44 (CD44) was observed mainly on T cells and macrophages and expression of intercellular adhesion molecules-1 (ICAM-1) was observed on sinusoidal endothelial cells (SEC). T cells were in contact with SEC or hepatocytes and shedding of hepatocyte was found by electron microscopy. On the other hand, by injection of recombinant mouse TNF alpha the numbers of enlarged macrophages were increased in the liver parenchyma but the necrosis of hepatocytes was not apparent. Expression of LFA-1 and CD44 was mainly observed on macrophages and expression of ICAM-1 was found on SEC. Activated macrophages were observed in contact with SEC or hepatocytes by electron microscopy. No expression of ICAM-1 on interlobular bile duct epithelia was observed in any groups. This study suggests that the expression of adhesion molecules play an important role in developing hepatic GVHD. TNF alpha appeared to be one of the factors which deteriorate hepatic GVHD through an activation of macrophages and expression of adhesion molecules.
Hayashishita
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Third Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D000818:Animals; D016026:Bone Marrow Transplantation; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008107:Liver Diseases / Q000276:immunology*; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1