3-nitrotyrosine and Leprosy

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.

Topics: Animals; Chronic Disease; Cyclooxygenase 2; Female; Granuloma; Immunohistochemistry; Leprosy; Mice; Mice, Inbred Strains; Models, Animal; Mycobacterium lepraemurium; Nitric Oxide Synthase Type II; Orosomucoid; Staining and Labeling; Tyrosine

Nerve damage is a common and disabling feature of leprosy, with unclear aetiology. It has been reported that the peroxidizing agents of myelin lipids-nitric oxide (NO) and peroxynitrite-are produced in leprosy skin lesions.. To investigate the localization of nitrotyrosine (NT)-a local end-product of peroxynitrite-in leprosy lesions where dermal nerves are affected by a granulomatous reaction.. We investigated by immunohistochemistry and immunoelectron microscopy the localization of the inducible NO synthase (iNOS) and NT in biopsies exhibiting dermal nerves from patients with untreated leprosy.. There were abundant NT-positive and iNOS-positive macrophages in the borderline leprosy granulomas infiltrating peripheral nerves identified by light microscopy, S-100 and neurofilament immunostaining. Immunoelectron microscopy showed NT reactivity in neurofilament aggregates and in the cell wall of Mycobacterium leprae.. Our results suggest that NO and peroxynitrite could be involved in the nerve damage following borderline leprosy.

Topics: Granuloma; Humans; Immunohistochemistry; Leprosy; Macrophages; Microscopy, Immunoelectron; Mycobacterium leprae; Nitric Oxide Synthase; Peripheral Nerves; S100 Proteins; Skin; Skin Diseases, Bacterial; Tyrosine