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Isolation and Culture of Primary Synovial Macrophages and Fibroblasts from Murine Arthritis Tissue
Published on: February 24, 2023
Apoptosis in rheumatoid arthritis synovium
G S Firestein1, M Yeo, N J Zvaifler
1University of California, San Diego Medical Center, La Jolla, California 92093, USA.
The Journal of Clinical Investigation
|September 1, 1995
Summary
Apoptosis, or programmed cell death, occurs in rheumatoid arthritis (RA) synovial tissue, primarily in lining cells like macrophages. Specific cytokines regulate this process, potentially contributing to RA pathogenesis.
Area of Science:
- Rheumatology
- Cell Biology
- Immunology
Background:
- Rheumatoid arthritis (RA) is characterized by synovial tissue (ST) inflammation.
- The role and location of apoptosis in RA ST remain incompletely understood.
Purpose of the Study:
- To investigate the occurrence and localization of apoptosis in RA synovial tissue.
- To identify the cell types undergoing apoptosis and the factors regulating this process.
Main Methods:
- Genomic DNA extraction and agarose gel electrophoresis to detect DNA ladders.
- In situ end-labeling (ISEL) to identify DNA strand breaks in frozen tissue sections.
- Combined immunohistochemistry and ISEL to characterize apoptotic cells.
- Flow cytometry to assess Fas expression on cultured synoviocytes.
Main Results:
- DNA ladders indicative of apoptosis were found in RA ST samples.
- ISEL confirmed DNA strand breaks in RA ST, predominantly in synovial lining cells (macrophages and fibroblasts).
- T cells in lymphoid aggregates were spared from apoptosis, showing high bcl-2 expression.
- Apoptosis in cultured synoviocytes was induced by actinomycin D, anti-Fas antibody, IL-1, and TNF-alpha, but not IFN-gamma.
Conclusions:
- DNA strand breaks and apoptosis are present in the synovium of patients with arthritis.
- Cytokines, particularly the RA-associated profile (high IL-1/TNF, low IFN-gamma), likely regulate apoptosis in RA ST.
- Local oxidant injury may also contribute to apoptosis induction in RA.
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