Accumulation of matrilysin (MMP-7) and macrophage metalloelastase (MMP-12)in actinic damage

Photodamage is characterized by degradation of collagen and accumulation of abnormal elastin in the superficial dermis and several matrix metalloprote inases have previously been implicated in this process. Using immunohistoch emistry and in situ hybridization, we have studied the localization of two elastolytic matrix metalloproteinases, matrilysin (matrix metalloproteinase -7) and human macrophage metalloelastase (matrix metalloproteinase-12) in s olar damage. Human macrophage metalloelastase protein was detected in the s uperficial dermis in areas of elastotic material. Matrix metalloproteinase- 7 was seen in the mid-dermis in regions with less damaged elastic fibers an d morphologically better preserved collagen as well as in a band-like patte rn below basal keratinocytes in eight of 18 solar elastosis. In samples tak en from healthy volunteers 3 d after repeated ultraviolet A or ultraviolet B photoprovocation, occasional immunopositive cells for human macrophage me talloelastase (stromal) or matrix metanoproteinase-7 (sweat gland epitheliu m) were detected. In samples taken 1 d after ultraviolet B exposure, howeve r, basal keratinocytes were matrix metalloproteinase-7 immunopositive, expl aining the linear immunostaining below basal keratinocytes noted particular ly in ultraviolet B treated 3 d specimens. Upregulation of metalloelastase was also demonstrated in the skin of hairless mice after repeated ultraviol et exposure. In normal skin, no staining for human macrophage metalloelasta se or matrix metalloproteinase-7 was observed in association with elastin. The amount of immunoreactivity for the substrates of matrix metalloproteina se-7, versican, and tenascin, was clearly increased in solar elastosis and photoprovocated skin; versican but not tenascin was detected in the same ar eas as matrix metalloproteinase-7. Our results suggest that both matrix met alloproteinase-7 and -12 may contribute to remodeling of elastotic areas in sun-damaged skin.