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In order to investigate the properties of collagen in chronically inflamed tissue, we isolated collagen from the ear skin of mice with chronic contact dermatitis and examined its biochemical characteristics and the functions that regulate the secretion of matrix metalloproteinase 2 and collagen-degrading enzymes from endothelial cells and fibroblasts. Collagen in skin with chronic contact dermatitis comprised 60% type I collagen and 40% type III collagen, which latter is higher than the content of type III collagen in control skin (35%). The denaturation temperature was higher (42 degrees C) than that of control skin (39 degrees C). The alpha2 chain of type I collagen was over-hydroxylated at both proline and lysine residues. Segment-long-spacing crystallites of type I collagen were unusually connected in tandem. Collagen of chronically inflamed skin was less susceptible to matrix metalloproteinase 2 after heat denaturation. Endothelial cells and fibroblasts secreted an increased amount of matrix metalloproteinase 2 when cultured on a gel formed from the collagen of chronically inflamed skin. Collagen-degrading activity secreted from fibroblasts was also upregulated when cells were in contact with collagen of chronically inflamed skin. These results suggest that the collagen in chronically inflamed tissue has altered biochemical characteristics and functions, which may affect the pathogenesis of the chronic skin disease.

Recently it has been reported that the molecular size of decorin dermatan sulfate (DS) was increased in healing skin after hapten application and that the elongated DS was distributed in enlarged interfibrillar space among thin collagen fibrils in situ. Here we show that such modulation of the length of decorin DS is temporary. Although the size of decorin DS was evidently increased on day 15, it decreased to almost normal size on day 35 when the altered disaccharide composition of DS was also recovered. Electron microscopic observation revealed that elongated decorin DS was localized among thin collagen fibrils packed loosely in hapten-treated skin on day 15. In contrast, decorin DS of normal size was distributed among thick collagen fibrils packed tightly on day 35. These results suggest that size control of decorin DS plays important roles in organization of collagen fibrils into bundles by regulating interfibrillar space in healing skin, particularly in maturation of collagen fibrils through shortening of decorin DS in later stages of healing.

Transmissible spongiform encephalopathies are characterized by the accumulation of a proteinase-resistant isoform of the cellular prion-related protein (PrP(c)) within the central nervous system (CNS). The accumulation of scrapie-associated PrP (PrP(Sc)) within cells of the lymphoreticular system prior to its accumulation in the CNS is regarded as important for the development of neurological diseases after peripheral inoculation. Little, however, is known as to which cells are the targets for peripheral inoculation. Here, the presence of PrP(c) on murine Langerhans cells (LC), dendritic cells in the skin and mucosa, and keratinocytes (KC) is demonstrated by immunohistochemical staining, Western-blotting and FACS analysis. The expression of PrP(c) mRNA in freshly purified LC and KC was also detected by reverse transcriptase-polymerase chain reaction. The expression of PrP(c) on LC was slightly increased during culture. These data suggest that LC and KC may be the targets for peripheral infection with prions.