Variations of neuronal nitric oxide synthase in systemic sclerosis skin.
OBJECTIVE
In systemic sclerosis (SSc), derangement of the peripheral nervous system is linked to vascular tone dysfunction. Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS, NOS-I) might play a dynamic role in the control of vascular tone. This study was performed to verify, by immunohistochemical and biochemical analyses, the presence and expression of nNOS and protein gene product 9.5 (PGP 9.5) in SSc skin, in different subsets and various phases of the disease.


METHODS
Biopsy samples of clinically involved skin from 32 SSc patients (12 with limited cutaneous SSc [lcSSc] and 20 with the diffuse form [dcSSc]) and skin samples from 6 healthy controls were either immunostained with anti-PGP 9.5 and anti-nNOS antibodies or analyzed by semiquantitative reverse transcription-polymerase chain reaction and Western blotting.


RESULTS
Immunohistochemical and biochemical data showed a decrease in PGP 9.5 and nNOS innervation and in their messenger RNA (mRNA) levels in lcSSc and dcSSc skin. In the edematous phase of SSc, a light alteration in cutaneous innervation was initiated and slowly progressed into the sclerotic phase, becoming most evident in the atrophic phase. Levels of nNOS mRNA were significantly lower between the edematous phase and the sclerotic phase in both dcSSc and lcSSc skin, which was attributable to the earlier occurrence of more severe pathologic alterations.


CONCLUSIONS
Total cutaneous innervation and nNOS innervation slowly disappear in the skin of SSc patients. Expression of nNOS depends on the severity of tissue damage in SSc, and increased synthesis of NO also contributes to this process. It remains to be determined whether the changes in cutaneous innervation are due to the disease itself or whether these changes contribute to the pathogenesis and evolution of SSc.
Ibba-Manneschi
Lidia
L
Dept. of Anatomy, Histology and Forensic Medicine, University of Florence, Viale G.B. Morgagni 85, 50134 Florence, Italy. ibba@unifi.it
Niissalo
Sirkku
S
Milia
Anna Franca
AF
Allanore
Yannick
Y
Del Rosso
Angela
A
Pacini
Alessandra
A
Manetti
Mirko
M
Toscano
Annarita
A
Cipriani
Paola
P
Liakouli
Vasiliki
V
Giacomelli
Roberto
R
Kahan
André
A
Konttinen
Yrjö T
YT
Matucci-Cerinic
Marco
M
D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D012867:Skin / Q000201:enzymology* / Q000473:pathology
D052248:Nitric Oxide Synthase Type I