N-desulfated heparin improves concanavalin A-induced liver injury partly through inhibiting T lymphocyte adhesion

Objective and Design: To examine the effect of N-desulfated heparin on Concanavalin A (Con A)-induced liver injury and its mechanisms of action. Materials and methods: Liver injury was induced in mice by Con A. The in vitro assays for examining the adhesions of spleen T lymphocytes and Jurkat cells to extracellular matrix (ECM) were also performed. Results: N-desulfated heparin significantly inhibited the elevation in alanine transaminase, aspartate transaminase and lactic dehydrogenase activities in serum, and recovered the superoxide dismutase activity in the liver tissue of mice with liver injury. In liver histological examination, the inflammatory infiltration, hepatocyte degeneration and Kupffer cell hyperplasia were remarkably improved by N-desulfated heparin. Multiple administrations of the heparin derivative for one day showed a more potent prevention of the liver injury than did single dosing for three days. N-desulfated heparin significantly inhibited the adhesion of spleen cells and purified T lymphocytes isolated from the liver injured mice to either type I collagen or fibronectin but not to laminin. The heparin derivative also showed a similar inhibition of the adhesion of spleen cells from normal mice, stimulated in vitro with Con A, whereas it did not affect their proliferation. Moreover, the adhesion of human leukemia Jurkat cells to collagen I was inhibited by N-desulfated heparin. Conclusion: N-desulfated heparin may improve immunological liver injury partly via reducing the functions, such as the adhesion to ECM, of T lymphocytes.