title: Increased immunostaining of collagenase and TIMP in eruptive xanthoma.
abstract: Remodeling of the extracellular matrix is an important function of interstitial collagenase. The activity of this enzyme forms the initial and rate limiting step in collagen degradation; moreover, this enzyme appears representative of a family of connective tissue metalloproteinases. Conversely, a widely distributed glycoprotein, tissue inhibitor of metalloproteinases (TIMP), may be an important regulator of matrix degradation. To study the roles of collagenase and TIMP in pathologically altered dermal connective tissue, immunohistochemistry was used to localize collagenase and TIMP in an eruptive xanthoma, a chronic tuberous xanthoma, and normal skin. Normal skin and the chronic tuberous xanthoma showed mild diffuse staining of both proteins throughout the dermis. In contrast, intense dermal staining of both collagenase and TIMP was present in the eruptive xanthoma. Thus, the marked accumulation of lipid in dermal macrophages was associated with a significant increase in matrix collagenase and TIMP. This increase may reflect direct production of these two proteins by macrophages. Alternatively, it may be due to increased production by fibroblasts stimulated by macrophage-derived cytokines. The balance of degradative and inhibitory activities in the extracellular matrix may regulate the extent and nature of dermal remodeling.
authors: Section of Dermatology, Medical Service VA Medical Center, Nashville, TN 37212.
authors: J W
authors: JW
authors: Childers
authors: G P
authors: GP
authors: Stricklin
mesh_terms: D004791:Enzyme Inhibitors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008666:Metalloendopeptidases; D003012:Microbial Collagenase / Q000378:metabolism*; D012016:Reference Values; D013194:Staining and Labeling; D019714:Tissue Inhibitor of Metalloproteinases; D014973:Xanthomatosis / Q000378:metabolism* / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases; D003012:Microbial Collagenase