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.
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.
Authors: James J Farrell; Douglas Taupin; Theodore J Koh; Duan Chen; Chun-Mei Zhao; Daniel K Podolsky; Timothy C Wang Journal: J Clin Invest Date: 2002-01 Impact factor: 14.808
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Authors: Carlos Felipe Bernardes-Silva; Adérson O M C Damião; Aytan M Sipahi; Francisco R M Laurindo; Kiyoshi Iriya; Fabio P Lopasso; Carlos A Buchpiguel; Maria Laura L Lordello; Carmem L O Agostinho; Antonio A Laudanna Journal: Dig Dis Sci Date: 2004-10 Impact factor: 3.199
Authors: George C Nadăş; Marian A Taulescu; Lidia Ciobanu; Nicodim I Fiţ; Chirilă Flore; Sorin Răpuntean; Cosmina M Bouari; Cornel Catoi Journal: Mycopathologia Date: 2013-01-19 Impact factor: 2.574