LEA-1/ICAM-1 interaction is essentially involved in the pathogenesis of delayed-type hypersensitivity-induced liver injury to picryl chloride.
The kinetics of lymphocyte function associated antigen 1 (LFA-1) expression on spleen cells (SPC) and liver non-parenchymal cells (NPC), and intercellular adhesion molecule 1 (ICAM-1) expression on hepatocytes (HC) was examined in acute liver injury mice induced by a DTH reaction to picryl chloride (PCl). The peak expression of LFA-1 on SPC was seen at 6 hr after eliciting liver injury, and then that of LFA-1 on NPC and ICAM-1 on HC appeared at 12 hr. Thereafter, the serum ALT elevation reached to a peak at 18 hr. A splenectomy before the PCl elicitation significantly reduced the ALT elevation. Both SPC and NPC from liver injury mice induced a remarkable release of ALT from HC in vitro, in parallel with their LFA-1 expression. The pre-treatment of NPC or SPC with anti-LFA-1 mAb, irrespective of the presence of complement, completely blocked the ALT release. Also, when HC was prebound with anti-ICAM-1 mAb, neither NPC nor SPC showed a cytotoxicity against the HC. Furthermore, the treatment of NPC with either anti-Thy1.2 or anti-CD4 mAb in the presence but not absence of complement, showed a complete abolishment of ALT release. Anti-CD8 mAb plus complement also tended to inhibit ALT release. The twofold increase in CD4+ LFA-1+ and mild increase in CD8+ LFA-1+ populations were also confirmed in NPC at 12 hr. These results suggest that PCl elicitation in liver may trigger an increased expression of LFA-1 on SPC and NPC and ICAM-1 on HC. LFA-1/ICAM-1 interaction between liver-infiltrating NPC, mainly including CD4+ and CD8+ T cells, and HC may be an essential step for the hepatocyte damage in PCl-DTH liver injury.
Xu
Q
Q
Department of Pharmacology for Chinese Materia Medica, China Pharmaceutical University, Nanjing, The People's Republic of China.
Jiang
J
J
Cao
J
J
Wu
F
F
Fujii
H
H
Saiki
I
I
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010853:Picryl Chloride / Q000633:toxicity*; D013154:Spleen / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D000410:Alanine Transaminase; D010853:Picryl Chloride