HUMAN SPASMOLYTIC POLYPEPTIDE IS A CYTOPROTECTIVE AGENT THAT STIMULATES CELL-MIGRATION

Background/Aims: Gastric epithelium is attacked by acid, pepsin, and i ngested agents. When a mucosal lesion occurs, the defect is rapidly cl osed by cell migration. Because spasmolytic polypeptide is rapidly pro duced at sites of injury, we postulated that human spasmolytic polypep tide (hSP) was important in mucosal repair. Recombinant hSP was used t o test this hypothesis. Methods: The ulcer healing effect of various d oses of hSP administered orally and subcutaneously was examined using an indomethacin (20 mg/kg) restraint rat model of gastric damage. Stab ility of hSP in gastrointestinal juice was determined using size-exclu sion chromatography. The effect of hSP on migration of human colonic c arcinoma cell lines HT29 and SW480 was determined using collagen gel i nvasion and wounded monolayer assays. Proliferation was assessed using [H-3]thymidine incorporation and toluidine blue staining. Results: In fusions of hSP at 25 and 50 mu g.kg(-1).h(-1) subcutaneously decreased gastric damage by about 50% (P < 0.01) without changing acid secretio n. Oral hSP was ineffective. hSP was stable in gastrointestinal juice. hSP stimulated migration of HT29 cells but did not affect proliferati on and had no effect on SW480 cells. Conclusions: hSP may play a key r ole in the early stages of mucosal repair by stimulating the initial r e-epithelialization by cell migration.