02430nas a2200325 4500000000100000008004100001260001300042653001100055653001100066653002800077653002400105653002500129653001700154653002600171653003400197653002300231653000900254653001300263100001300276700002400289700001400313700001500327700001600342700001400358245009900372300001100471490000800482520160000490022001402090 2001 d c2001 Nov10aBiopsy10aHumans10aImmunoenzyme Techniques10aLeprosy, Borderline10aLeprosy, Tuberculoid10aNitric Oxide10aNitric Oxide Synthase10aNitric Oxide Synthase Type II10aPeroxynitrous Acid10aSkin10aTyrosine1 aSchön T1 aHernandez-Pando R H1 aNegesse Y1 aLeekassa R1 aSundqvist T1 aBritton S00aExpression of inducible nitric oxide synthase and nitrotyrosine in borderline leprosy lesions. a809-150 v1453 a
BACKGROUND: In the response to T-helper cell (Th1)-type cytokines and interactions with pathogens, high levels of nitric oxide (NO) are produced by activated macrophages expressing the inducible NO synthase (iNOS). The role and importance of reactive nitrogen intermediates (RNIs) such as NO and peroxynitrite in the host response to diseases caused by intracellular pathogens such as Mycobacterium leprae and M. tuberculosis is unclear.
OBJECTIVES: The aim of this study was to investigate the presence of local production of NO and peroxynitrite in borderline leprosy by using antibodies against iNOS and the product of peroxynitrite, nitrotyrosine (NT).
METHODS: We detected the presence of iNOS and NT in skin biopsies from borderline leprosy patients, with and without reversal reaction (RR), by immunohistochemistry (n = 26).
RESULTS: In general, the granulomas from borderline leprosy lesions with and without RR showed high and specific expression of iNOS and NT. Moreover, strong immunoreactivity to iNOS and NT was observed in granulomas surrounding and infiltrating dermal nerves. The expression of iNOS and NT was also strong in keratinocytes, fibroblasts and endothelial cells in close relation to the granulomatous reaction. In contrast, normal human skin showed no expression of iNOS and NT in these cells.
CONCLUSIONS: We conclude that iNOS and NT are expressed in granulomas from borderline leprosy patients with and without RR and propose that RNIs might be involved in the nerve damage following RR in leprosy.
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