02606nas a2200349 4500000000100000008004100001260001300042653001200055653002000067653002100087653001100108653001400119653002500133653001200158653000900170653002500179653001900204653003100223653003400254653001600288653002600304653001300330100002000343700001800363700002400381700002100405245014300426300001100569490000700580520165500587022001402242 2006 d c2006 Dec10aAnimals10aChronic Disease10aCyclooxygenase 210aFemale10aGranuloma10aImmunohistochemistry10aleprosy10aMice10aMice, Inbred Strains10aModels, Animal10aMycobacterium lepraemurium10aNitric Oxide Synthase Type II10aOrosomucoid10aStaining and Labeling10aTyrosine1 aSilva Miranda M1 aRodríguez KW1 aMartínez Cordero E1 aRojas-Espinosa O00aExpression of cyclooxygenase-2, alpha 1-acid-glycoprotein and inducible nitric oxide synthase in the developing lesions of murine leprosy. a485-940 v873 a

Murine leprosy is a chronic disease of the mouse, the most popular animal model used in biomedical investigation, which is caused by Mycobacterium lepraemurium (MLM) whose characteristic lesion is the macrophage-made granuloma. From onset to the end of the disease, the granuloma undergoes changes that gradually transform the environment into a more appropriate milieu for the growth of M. lepraemurium. The mechanisms that participate in the formation and maturation of the murine leprosy granulomas are not completely understood; however, microbial and host-factors are believed to participate in their formation. In this study, we analysed the role of various pro-inflammatory and anti-inflammatory proteins in granulomas of murine leprosy after 21 weeks of infection. We assessed the expression of cyclooxygenase-2 (COX-2), alpha acid-glycoprotein (AGP), and inducible nitric oxide synthase (iNOS) at sequential stages of infection. We also looked for the nitric-oxide nitrosylation product, nitrotyrosine (NT) in the granulomatous lesions of murine leprosy. We found that a pro-inflammatory environment predominates in the early granulomas while an anti-inflammatory environment predominates in late granulomas. No obvious signs of bacillary destruction were observed during the entire period of infection, but nitrosylation products and cell alterations were observed in granulomas in the advanced stages of disease. The change from a pro-inflammatory to an anti-inflammatory environment, which is probably driven by the bacillus itself, results in a more conducive environment for both bacillus replication and the disease progression.

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