ADHESION MOLECULES ON INTERMEDIATE TCR CELLS .2. HEPATOPROTECTIVE EFFECTS OF HYALURONIC-ACID ON ACUTE LIVER-INJURY

The liver is a major organ wherein extrathymic T cells and NK cells ex ist in mice. Due to their unique properties, i.e., extrathymic T cells are TCR (or CD3)-intermediate+ IL-2R beta(+) (herein termed intermedi ate TCR cells) and NK cells are TCR(-)IL-2R beta(+), they are easily d istinguished from the other lymphocyte subsets by using mAbs in conjun ction with immunofluorescence tests. They were recently found to expre ss a higher level of CD44 antigen, which is a ligand for hyaluronic ac id, than that of another T cell subset (i.e., thymus-derived T cells o r bright TCR cells). Since an intravenous administration of hyaluronic acid was also found to reduce the number of intermediate TCR cells an d NK cells in the liver, we examined whether hyaluronic acid had a hep atoprotective effect on acute liver injury. Such injury was induced by LPS injection in mice pretreated with Propionibacterium acnes 1 week earlier. When a single dose of hyaluronic acid was given to these mice 12 hr before LPS injection, a prominent hepatoprotective effect was o bserved in terms of decreases of mortality (up to 50%), lymphocyte inf iltration of the liver, serum transaminase levels, and tissue damage. At this time, liver mononuclear cells isolated from the treated mice s howed decreased levels of cytokine production such as TNF and IL-1. Th ese results reveal that intermediate TCR cells and Nh cells in the liv er actually adhere the sinusoid walls by means of an interaction of CD 44 molecules and hyaluronic acid even in the case of acute liver injur y. It suggests a possible therapeutic effect of the administration of hyaluronic acid in acute liver injury by eliminating the effector cell s and cytokine-producing cells from the liver. (C) 1995 Academic Press , Inc.