Expression of inducible nitric oxide synthase and nitrotyrosine in borderline leprosy lesions.
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.


OBJECTIVE
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.
Schön
T
T
Department of Medical Microbiology, Faculty of Health Sciences, 581 85 Linköping, Sweden. thosc@ihm.liu.se
Hernandez-Pando
R H
RH
Negesse
Y
Y
Leekassa
R
R
Sundqvist
T
T
Britton
S
S
D001706:Biopsy; D006801:Humans; D007124:Immunoenzyme Techniques; D015439:Leprosy, Borderline / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D015441:Leprosy, Tuberculoid / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000096:biosynthesis; D012867:Skin / Q000201:enzymology / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II