Non-peptidic analogs of the cell adhesion motif RGD prevent experimental liver injury

In chronic viral hepatitis, autoimmune hepatitis, and some chronic cholesta tic liver diseases, T lymphocytes serve as effector cells of the immunostim ulatory processes. Cellular interactions of immune cells with extracellular matrix components are regulated primarily via the beta(1) subfamily of int egrin receptors. The target epitope of several such integrin receptors is t he Arg-Gly-Asp sequence, a cell adhesion motif shared Gy several matrix-ass ociated adhesive glycoproteins. We review the use of synthetic nonpeptidic analogs of RGD in the prevention of immune-mediated, concanavalin A-induced liver damage in mice and in inhibiting the development of liver cirrhosis in rats. The Con A-induced elevation of serum transaminases and tumor necro sis factor-alpha and the infiltration of liver tissue by inflammatory cells were inhibited by pretreatment of the mite with the synthetic RGD mimetics . In rats, the progression of thioacetamide-induced liver cirrhosis was mar kedly inhibited by the co-administration of the RGD mimetic SF-6,5. The com pounds described here may be examined therapeutically for pathological cond itions in the liver. manifested as necro-inflammation and fibrosis.