Indomethacin induced gastropathy in CD18, intercellular adhesion molecule 1, or P-selectin deficient mice.
BACKGROUND
Neutrophil-endothelial cell interactions are thought to play a critical role in the pathophysiology of non-steroidal anti-inflammatory drug (NSAID) induced gastropathy.


OBJECTIVE
To optimise a mouse model of NSAID induced gastropathy and to evaluate the importance of adhesion molecules using adhesion molecule deficient mice.


METHODS
Gastropathy was induced in C57BL/6 mice or their adhesion molecule deficient counterparts via oral administration of indomethacin (20 mg/kg). Lesion scores, mucosal permeability, and histopathology were used to assess gastric mucosal injury.


RESULTS
Intragastric administration of indomethacin induced linear haemorrhagic mucosal lesions, primarily in the corpus of the stomach that were first observed at six hours. These lesions continued to develop over the next six hours with maximal lesion scores and mucosal permeabilities at 12 hours. When indomethacin was administered to mice deficient in CD18, intercellular adhesion molecule 1 (ICAM-1), or P-selectin, there were significant decreases in lesion scores compared with their C57BL/6 controls. In addition, mucosal permeabilities were found to be significantly lower in CD18 or ICAM-1 deficient mice observed at 12 hours.


CONCLUSIONS
Certain leucocyte and endothelial cell adhesion molecules are important determinants for full expression of indomethacin induced gastropathy. It is proposed that this modification of the mouse model may be useful for the investigation of other pathophysiological mechanisms of NSAID induced gastropathy.
Morise
Z
Z
Department of Molecular and Cellular Physiology, LSU Medical Centre, Shreveport, Louisiana, USA.
Granger
D N
DN
Fuseler
J W
JW
Anderson
D C
DC
Grisham
M B
MB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D018821:CD18 Antigens / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D013272:Stomach Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016861:Cyclooxygenase Inhibitors; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D007213:Indomethacin