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Upregulation of complement regulators MCP (CD46), DAF (CD55) and protectin (CD59) in arthritic joint disease
M E Davies1, A Horner, B E Loveland
1Strangeways Research Laboratory, Worts Causeway, Cambridge, UK.
Insights
Complement regulatory proteins CD46, CD55, and CD59 are upregulated in inflammatory joint diseases. This suggests their elevated levels protect chondrocytes from complement-mediated damage in arthritis.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- CD46, CD55, and CD59 are cell surface glycoproteins crucial for preventing complement-mediated damage in normal tissues.
- Inflammatory conditions can alter the expression of these protective molecules.
Purpose of the Study:
- To investigate the expression patterns of CD46, CD55, and CD59 in cartilage under inflammatory conditions.
- To compare molecule expression in IL1-stimulated cartilage and diseased arthritic joints versus normal cartilage.
Main Methods:
- Immunocytochemical techniques were employed to analyze protein expression.
- Experiments were conducted both in vitro (IL1-stimulated chondrocytes in culture) and in vivo (arthritic joints).
- Human and pig tissues were utilized for comparative analysis.
Main Results:
- A marked but disparate upregulation of CD46, CD55, and CD59 was observed in IL1-treated cartilage and arthritic cartilage compared to normal cartilage.
- Expression of these proteins was localized to the chondrocyte surface.
- Upregulation was confirmed in isolated chondrocytes stimulated with IL1 in monolayer culture.
Conclusions:
- Elevated levels of CD46, CD55, and CD59 on chondrocytes may serve a protective role in inflammatory joint diseases.
- These regulatory proteins likely help mitigate the damaging effects of complement activation in conditions like arthritis.
- The findings highlight the complex interplay between complement regulation and inflammatory joint pathology.
Abstract:
CD46, CD55 and CD59 are cell surface glycoproteins which are widely distributed on normal tissue, where they function in the prevention of complement-mediated damage. In this study we have investigated the altered expression of these molecules under inflammatory conditions both in vitro and in vivo. By using immunocytochemical techniques we demonstrated marked but disparate upregulation of these molecules in IL1-treated cartilage and in diseased cartilage from arthritic joints compared to normal cartilage in both humans and pigs. Expression of these proteins was restricted to the chondrocyte surface, and was also demonstrated on isolated chondrocytes grown in monolayer culture and stimulated with IL1. It is suggested that the elevated levels of these regulatory proteins may be necessary to ameliorate the multiple damaging effects of the inflammatory processes associated with destructive joint diseases.