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Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and macrophage migration
M Vaalamo1, A L Kariniemi, S D Shapiro
1Department of Dermatology, Helsinki University Central Hospital, Finland.
Abstract:
Accumulation of inflammatory cells such as macrophages may lead to degeneration of connective tissue matrix in various skin diseases. Macrophage metalloelastase, is a matrix metalloproteinase (MMP-12) capable of degrading elastin as well as various basement membrane components. To investigate the role of human macrophage metalloelastase in skin, we assessed by in situ hybridization and immunohistochemistry 66 specimens representing skin diseases characterized either by changes in elastic fibers or by pronounced infiltrations of extravasating and migrating macrophages. CD68 immunostaining was performed to identify the human macrophage metalloelastase-positive cells and Weigert's Resorcin-Fuchsin staining to reveal the status of elastic fibers. We found abundant expression of human macrophage metalloelastase mRNA in macrophages in areas devoid of normal elastic fibers in granulomatous skin diseases sarcoidosis, necrobiosis lipoidica diabeticorum, and granuloma annulare. Positive cells for human macrophage metalloelastase protein could be detected in the same regions as well as positive immunostaining for urokinase plasminogen activator. Of the other matrix metalloproteinases capable of degrading elastin, 92 kDa gelatinase colocalized with human macrophage metalloelastase, while 72 kDa gelatinase was produced by surrounding fibroblast-like cells. Furthermore, human macrophage metalloelastase was expressed by macrophages in areas with disrupted basement membrane, as assessed by type IV collagen staining, in pityriasis lichenoides and dermatitis herpetiformis. Specimens of anetoderma, acrodermatitis chronica atrophicans and pseudoxanthoma elasticum showed no signal for human macrophage metalloelastase. Matrilysin was not detected in any of the samples investigated. Our study suggests that human macrophage metalloelastase may contribute to elastin degradation occurring in granulomatous skin diseases and may aid macrophage migration through the epidermal and vascular basement membranes in inflammatory disorders.
Insights
Human macrophage metalloelastase (MMP-12) aids in degrading elastic fibers and basement membranes in inflammatory skin diseases. Its expression is linked to granulomatous conditions and macrophage migration, but not all atrophic skin disorders.
Area of Science:
- Dermatology
- Immunology
- Biochemistry
Background:
- Macrophages accumulate in skin diseases, potentially degrading connective tissue.
- Macrophage metalloelastase (MMP-12) degrades elastin and basement membrane components.
Purpose of the Study:
- Investigate the role of human macrophage metalloelastase (MMP-12) in various skin diseases.
- Correlate MMP-12 expression with elastic fiber status and basement membrane integrity.
Main Methods:
- In situ hybridization and immunohistochemistry on 66 skin specimens.
- CD68 staining for macrophages, Weigert's Resorcin-Fuchsin for elastic fibers, and type IV collagen for basement membranes.
- Analysis of MMP-12, urokinase plasminogen activator, and other matrix metalloproteinases.
Main Results:
- MMP-12 mRNA and protein abundant in macrophages in granulomatous skin diseases (sarcoidosis, necrobiosis lipoidica diabeticorum, granuloma annulare) with elastic fiber loss.
- MMP-12 colocalized with 92 kDa gelatinase; 72 kDa gelatinase produced by fibroblasts.
- MMP-12 expressed by macrophages in areas of basement membrane disruption in pityriasis lichenoides and dermatitis herpetiformis.
- No MMP-12 signal in anetoderma, acrodermatitis chronica atrophicans, or pseudoxanthoma elasticum.
Conclusions:
- Human macrophage metalloelastase (MMP-12) likely contributes to elastin degradation in granulomatous skin diseases.
- MMP-12 may facilitate macrophage migration across basement membranes in inflammatory skin disorders.