Abstract
1. The effects of acharan sulphate, a glycosaminoglycan isolated from the giant African snail Achatina fulica, on angiogenesis in the granulation tissue were analysed using an air pouch-type carrageenin-induced inflammation model in rats and a cotton thread-induced inflammation model in mice. 2. In the carrageenin-induced inflammation model in rats, intra-pouch injections of acharan sulphate (5 and 50 micro g) inhibited the pouch fluid accumulation and the granulation tissue formation as well as the angiogenesis in the granulation tissue at day 6 in a dose-dependent manner. 3. The inhibitory effects of acharan sulphate at 50 micro g on the pouch fluid accumulation and the leucocyte infiltration into the pouch fluid was not so effective as that of the cyclo-oxygenase inhibitor indomethacin at 100 micro g, but the inhibitory effects of acharan sulphate at 50 micro g on the granulation tissue formation and angiogenesis in the granulation tissue were almost the same as those of indomethacin at 100 micro g. 4. Acharan sulphate did not affect levels of vascular endothelial growth factor (VEGF) in the granulation tissue and in the pouch fluid at day 6, but indomethacin significantly lowered them. 5. In the cotton thread-induced inflammation model in mice, injections of acharan sulphate (10 micro g) at the site of the cotton thread implantation inhibited the granulation tissue formation and angiogenesis as indomethacin (20 micro g) did. Acharan sulphate (10 micro g) did not affect levels of VEGF in the cotton thread-induced granulation tissue at day 5, but indomethacin (20 micro g) significantly lowered them. 6. In culture of human vascular endothelial cells, acharan sulphate at 10 and 100 micro g ml(-1) inhibited VEGF-induced capillary tube formation. 7. These findings suggest that the inhibitory effect of acharan sulphate on angiogenesis in carrageenin- and cotton thread-induced granulation tissues is not due to the inhibition of VEGF protein induction, but is due to the inhibition of VEGF-induced vascular tube formation.