| First Author | Beck PL | Year | 2000 |
| Journal | Gastroenterology | Volume | 119 |
| Issue | 3 | Pages | 699-705 |
| PubMed ID | 10982764 | Mgi Jnum | J:64232 |
| Mgi Id | MGI:1888884 | Doi | 10.1053/gast.2000.16497 |
| Citation | Beck PL, et al. (2000) Mechanisms of NSAID-induced gastrointestinal injury defined using mutant mice. Gastroenterology 119(3):699-705 |
| abstractText | Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used agents that have a high incidence of gastrointestinal side effects resulting in significant morbidity and mortality. Leukocytes have been implicated in NSAID-induced injury, but the mechanisms are unclear. We established a murine model of NSAID-induced gastrointestinal damage to assess the roles of candidate gene products in the pathogenesis of this injury. Methods: Indomethacin-induced gastrointestinal injury was assessed in wild-type and several mutant murine lines. Leukocyte involvement was assessed by neutrophil depletion, impairment of recruitment (resulting from targeted disruption of fucosyltransferase VII [FTVII]), and the absence of mature T and B cells with the use of Rag 2(-/-) mice. Activation and oxygen free radicals were assessed using gp91(phox-/-) mice that exhibit normal leukocyte recruitment but are deficient in myeloid cell activation and oxygen free radical generation. Results: Impairment of leukocyte recruitment (FTVII(/-)) and neutrophil depletion resulted in more than a 50% reduction in NSAID-induced injury. However, mice deficient in mature T and B cells had NSAID-induced damage comparable to control mice. Leukocyte activation was required for NSAID-induced damage because the gp91(phox-/-) mice were less susceptible to NSAID injury than wild-type mice. Conclusions: In this murine model system, FTVII-dependent leukocyte recruitment, leukocyte activation via gp91(phox), and neutrophils are required for NSAID-induced gastrointestinal injury, whereas T and B cells are not essential. |
