desmosine and Skin-Diseases

Hairless (SKH-1) mice were mated with Beige (C57B/bb) mice to produce a hairless mouse deficient in neutrophil elastase (hhbb). These mice were exposed to 0.09J UVB irradiation for 5 months to see if neutrophil elastase was an important factor in elastin remodeling and development of solar elastoses. Analysis of peritoneal neutrophils confirmed that the hhbb mouse was deficient in elastase, retaining only 10% as much activity as the normal littermates (hhHb). Skin MPO activity was equally elevated in all the mice receiving UVB suggesting an equal influx of inflammatory cells. The absolute breaking strength of the skin in both the hhBb and hhbb mice was not altered by UVB treatment over the 5 month exposure period. Elastin quantitated biochemically as desmosine, or visualized histologically, was increased following UVB exposure in the normal mice. In the elastase deficient mice, however, the elastin fibers appeared to be unaffected by exposure to UVB irradiation at this level. The results suggest that neutrophil elastase is an important mediator in the development of solar elastosis resulting from continued exposure to UVB irradiation.

Topics: Animals; Chemotaxis, Leukocyte; Desmosine; Disease Models, Animal; Disease Progression; Elasticity; Elastin; Female; Male; Mice; Mice, Hairless; Neutrophils; Pancreatic Elastase; Skin; Skin Aging; Skin Diseases; Ultraviolet Rays; Up-Regulation

Abnormalities in the amount of skin elastin occur in several cutaneous disorders. The number of elastic fibers is increased in elastotic disorders such as pseudoxanthoma elasticum (PXE) and cutis rhomboidalis nuchae (actinic elastosis, AE) and is decreased in elastolytic disorders such as cutis laxa (CL). We describe a procedure to quantify desmosines and elastin in small amounts of skin using high-performance liquid chromatography (HPLC). Biopsies were obtained from normal, nonsolar exposed skin and from the lesional skin of patients with PXE, cutis rhomboidalis nuchae, and CL. Specimens were subjected to hot alkali treatment and the desmosines were released by acid hydrolysis and quantified by HPLC. The mean value for normal skin was 252 +/- 28 ng desmosines per milligram wet weight (SD, n = 5). The disorders of elastosis (PXE and AE) demonstrated a two- to fivefold increased content of desmosines. In contrast, the elastolytic disorder (CL) had only 20% of the normal content of desmosines. Furthermore, PXE and normal skin elastins had the same amount of desmosines per milligram purified elastin. This method could be used to evaluate the extent of elastosis or elastolysis in a particular lesion.

Topics: Adult; Aged; Amino Acids; Chromatography, High Pressure Liquid; Cutis Laxa; Desmosine; Elastin; Humans; Isodesmosine; Middle Aged; Pseudoxanthoma Elasticum; Skin; Skin Diseases