Adhesion molecules on intermediate TCR cells. II. Hepatoprotective effects of hyaluronic acid on acute liver injury

The liver is a major organ wherein extrathymic T cells and NK cells exist in mice. Due to their unique properties, i.e., extrathymic T cells are TCR (or CD3)-intermediate+ IL-2R beta+ (herein termed intermediate TCR cells) and NK cells are TCR(-)IL-2R beta+, they are easily distinguished from the other lymphocyte subsets by using mAbs in conjunction with immunofluorescence tests. They were recently found to express a higher level of CD44 antigen, which is a ligand for hyaluronic acid, than that of another T cell subset (i.e., thymus-derived T cells or bright TCR cells). Since an intravenous administration of hyaluronic acid was also found to reduce the number of intermediate TCR cells and NK cells in the liver, we examined whether hyaluronic acid had a hepatoprotective 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 observed in terms of decreases of mortality (up to 50%), lymphocyte infiltration of the liver, serum transaminase levels, and tissue damage. At this time, liver mononuclear cells isolated from the treated mice showed decreased levels of cytokine production such as TNF and IL-1. These results reveal that intermediate TCR cells and NK cells in the liver actually adhere the sinusoid walls by means of an interaction of CD44 molecules and hyaluronic acid even in the case of acute liver injury. It suggests a possible therapeutic effect of the administration of hyaluronic acid in acute liver injury by eliminating the effector cells and cytokine-producing cells from the liver.