Monoclonal antibody against lymphocyte function-associated antigen 1 inhibits the formation of primary biliary cirrhosis-like lesions induced by murine graft-versus-host reaction.
Interaction between intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) might be involved in the pathogenesis of liver diseases. We investigated whether monoclonal antibodies (mAbs) against these two adhesion molecules could inhibit the formation of primary biliary cirrhosis (PBC)-like lesions in an animal model using graft-versus-host reaction (GVHR) with major histocompatibility complex class II disparity. PBC-like hepatic lesions such as cellular infiltration of portal area and nonsupprative destructive cholangitis (NSDC) were generated by injecting spleen T cells of C57BL/6 (B6) mice into (B6. C-H-2bm12 X B6) F1 mice. In the liver of these mice, increased number of LFA-1-positive cells and enhanced expression of ICAM-1 on sinusoidal endothelial cells and bile duct epithelial cells were observed immunohistochemically, when compared with F1 mice without GVHR. Hepatic lesions of these mAb-treated mice were almost completely inhibited in these mice compared with GVHR mice. Furthermore, we studied to determine which anti-LFA-1 mAb or anti-ICAM-1 mAb was essential to inhibit the hepatic lesions. Mice solely treated with anti-LFA-1 mAb showed significant inhibition of hepatic lesions, whereas treatment with anti-ICAM-1 mAb could not inhibit the lesions. Despite the inhibition of hepatic lesions, induction of GVHR and production of antimitochondrial antibodies were not impaired in mAb-treated mice. We conclude that LFA-1 mediates cell infiltration into the liver in this murine model of GVHR and suggest a possible therapeutic role of mAbs to this adhesion molecule in selective autoimmune liver diseases.
Kimura
T
T
Animal Center for Biomedical Research, Faculty of Medicine, University of Tokyo, Japan.
Suzuki
K
K
Inada
S
S
Hayashi
A
A
Isobe
M
M
Matsuzaki
Y
Y
Tanaka
N
N
Osuga
T
T
Fujiwara
M
M
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D005434:Flow Cytometry; D006087:Graft vs Host Reaction / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology; D013163:Splenomegaly / Q000473:pathology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D011768:Pyruvate Dehydrogenase Complex; D018799:Intercellular Adhesion Molecule-1