Human spasmolytic polypeptide is a cytoprotective agent that stimulates cell migration.
OBJECTIVE
Gastric epithelium is attacked by acid, pepsin, and ingested agents. When a mucosal lesion occurs, the defect is rapidly closed by cell migration. Because spasmolytic polypeptide is rapidly produced at sites of injury, we postulated that human spasmolytic polypeptide (hSP) was important in mucosal repair. Recombinant hSP was used to test this hypothesis.


METHODS
The ulcer healing effect of various doses of hSP administered orally and subcutaneously was examined using an indomethacin (20 mg/kg) restraint rat model of gastric damage. Stability of hSP in gastrointestinal juice was determined using size-exclusion chromatography. The effect of hSP on migration of human colonic carcinoma cell lines HT29 and SW480 was determined using collagen gel invasion and wounded monolayer assays. Proliferation was assessed using [3H]thymidine incorporation and toluidine blue staining.


RESULTS
Infusions of hSP at 25 and 50 micrograms.kg-1.h-1 subcutaneously decreased gastric damage by about 50% (P < 0.01) without changing acid secretion. Oral hSP was ineffective. hSP was stable in gastrointestinal juice. hSP stimulated migration of HT29 cells but did not affect proliferation and had no effect on SW480 cells.


CONCLUSIONS
hSP may play a key role in the early stages of mucosal repair by stimulating the initial re-epithelialization by cell migration.
Playford
R J
RJ
Department of Gastroenterology, Royal Postgraduate Medical School, London, England.
Marchbank
T
T
Chinery
R
R
Evison
R
R
Pignatelli
M
M
Boulton
R A
RA
Thim
L
L
Hanby
A M
AM
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D005750:Gastric Juice; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D007422:Intestines / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured
D036341:Intercellular Signaling Peptides and Proteins; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; C034407:pancreatic spasmolytic polypeptide; D003094:Collagen; D007213:Indomethacin