The inflammatory and cytotoxic effects of a nitric oxide releasing cream on normal skin

被引:60
作者
Ormerod, AD
Copeland, P
Hay, I
Husain, A
Ewen, SWB
机构
[1] Aberdeen Royal Infirm, Dept Dermatol, Aberdeen AB25 2ZN, Scotland
[2] Aberdeen Royal Infirm, Dept Pathol, Aberdeen AB25 2ZN, Scotland
关键词
acidified nitrite; adhesion molecules; apoptosis; p53;
D O I
10.1046/j.1523-1747.1999.00692.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
We describe the pro-inflammatory and cytotoxic effects of nitric oxide in vivo in human skin. Nitrite and ascorbic acid were mixed on the skin of 12 normal volunteers, three times daily, to release nitric oxide. Exposure to nitric oxide was varied by randomizing the concentration of nitrite and duration of application. Nitric oxide treated skin showed significant increases in cells expressing CD3, CD4, CD8, CD68, neutrophil elastase, ICAM-1, VCAM-1, nitrosotyrosine, p53, and apoptotic cells compared with skin treated with ascorbic acid alone. There was no significant increase in mast cells. Following application of nitric oxide there were significantly fewer CD1a positive Langerhans cells in the epidermis. These appeared to lose dendritic morphology and migrate from the epidermis. There was no significant difference in staining for Ki-67, a marker related to proliferating cell nuclear antigen, between active and control skin but staining was greater after exposure to higher dose nitric oxide than the low dose. Apoptosis, cytotoxicity, and p53 staining were relatively greater after 48 h exposure than after 24 h. These results suggest that nitric oxide is pro-inflammatory and is toxic to DNA, leading to the accumulation of p53 and subsequent apoptosis. High-dose nitric oxide paradoxically led to a smaller increase in macrophages and T cells than low dose suggesting an immunosuppressive effect of higher levels.
引用
收藏
页码:392 / 397
页数:6
相关论文
共 51 条
[1]   NITRIC-OXIDE - MEDIATOR, MURDERER, AND MEDICINE [J].
ANGGARD, E .
LANCET, 1994, 343 (8907) :1199-1206
[2]   Nitric oxide inhibits the secretion of T-helper 1- and T-helper 2-associated cytokines in activated human T cells [J].
Bauer, H ;
Jung, T ;
Tsikas, D ;
Stichtenoth, DO ;
Frolich, JC ;
Neumann, C .
IMMUNOLOGY, 1997, 90 (02) :205-211
[3]   SUBSTANCE-P AND NITRIC-OXIDE MEDIATE WOUND-HEALING OF ULTRAVIOLET PHOTODAMAGED RAT SKIN - EVIDENCE FOR AN EFFECT OF NITRIC-OXIDE ON KERATINOCYTE PROLIFERATION [J].
BENRATH, J ;
ZIMMERMAN, M ;
GILLARDON, F .
NEUROSCIENCE LETTERS, 1995, 200 (01) :17-20
[4]   A proinflammatory activity of interleukin 8 in human skin: Expression of the inducible nitric oxide synthase in psoriatic lesions and cultured keratinocytes [J].
BruchGerharz, D ;
Fehsel, K ;
Suschek, C ;
Michel, G ;
Ruzicka, T ;
KolbBachofen, V .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (05) :2007-2012
[5]   The role of nitric oxide in cell injury [J].
Brune, B ;
Messmer, UK ;
Sandau, K .
TOXICOLOGY LETTERS, 1995, 82-3 :233-237
[6]   Endothelial cell adhesion molecule expression and lymphocyte adhesion to endothelial cells: Effect of nitric oxide [J].
Cartwright, JE ;
Whitley, GSJ ;
Johnstone, AP .
EXPERIMENTAL CELL RESEARCH, 1997, 235 (02) :431-434
[7]   Involvement of the heme oxygenase carbon monoxide pathway in keratinocyte proliferation [J].
Clark, JE ;
Green, CJ ;
Motterlini, R .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 241 (02) :215-220
[8]  
De C.R., 1995, J CLIN INVEST, V96, P60
[9]  
FARUQI TR, 1997, AM J PHYSIOL, V273, pR2490
[10]  
FEELISH M, 1996, METHODS NITRIC OXIDE, P102