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In vivo Macrophage Imaging Using MR Targeted Contrast Agent for Longitudinal Evaluation of Septic Arthritis
Published on: October 20, 2013
[Macrophages in rheumatoid synovial membrane: an update]
1Université d'Oxford, Service d'Anatomie Pathologique, Centre Orthopédique Nuffield.
Abstract:
The immunophenotype of lining and subintimal synovial mononuclear phagocytes (MP) of rheumatoid arthritis (RA) were sought by immunohistology and compared with osteoarthritis (OA) tissue in order to determine the significance of MPs in the pathobiology of RA. Almost all the lining cells (SLCs) in RA consisted of MPs (80 to 90% expressing CD45/CD14/CD68). A major proportion of the interaggregate areas of the rheumatoid subintima was also made of MP cells (50 to 70% expressing CD14/CD68). A marked variation in the immunohistological reaction of antibodies reacting within intimal MPs and between intimal and subintimal MPs was found. Intimal MPs expressed a wide range of macrophage-associated antigens, including receptors for Fc (CD16, CD32, CD64) and complement (CD35, CD11b, CD11c) as well as several integrin and non-integrin cell adhesion molecules (CD29/CD49b, CD49d, CD49f, CD51/CD61, CD11a, CD31, CD54, CD44, CD9, CD63). The monocyte marker, CD14, was down-regulated on SLCs in both RA and OA. When compared to intimal expression of leucocyte common antigen (CD45), CD68, a pan-macrophage maturation antigen, was found to be an unreliable macrophage antigen in OA intima. There was no difference in antigenic phenotype of SLCs in inflammatory and non-inflammatory OA with early activation markers (CD25, CD71) mainly present on MPs. In RA, synovial MPs showed increased expression of activation, maturation and functional antigens suggesting that they are rapidly and fully activated. The fact that their recruitment was independent of the degree of lymphocyte infiltration further emphasises the central importance of synovial MPs in RA.
Insights
Synovial mononuclear phagocytes (MPs) are central to rheumatoid arthritis (RA) pathogenesis. These cells in RA exhibit heightened activation and maturation markers, indicating their critical role in the disease independent of lymphocyte infiltration.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial joint inflammation.
- Mononuclear phagocytes (MPs) are key immune cells implicated in inflammatory processes.
- The specific role and phenotype of MPs in RA pathogenesis require further elucidation.
Purpose of the Study:
- To investigate the immunophenotype of synovial lining and subintimal mononuclear phagocytes (MPs) in rheumatoid arthritis (RA).
- To compare the phenotype of MPs in RA with those in osteoarthritis (OA) to understand their significance in RA pathobiology.
Main Methods:
- Immunohistology was employed to analyze the expression of various cell surface antigens on synovial MPs.
- Antibodies were used to detect macrophage-associated antigens, cell adhesion molecules, and activation markers.
- The immunophenotype of MPs in RA synovial tissue was compared with that in OA synovial tissue.
Main Results:
- In RA, lining synovial cells (SLCs) were predominantly MPs (80-90%), as were cells in the subintima (50-70%).
- RA synovial MPs displayed a broad range of macrophage-associated antigens and cell adhesion molecules, with increased expression of activation and maturation markers compared to OA.
- The monocyte marker CD14 was downregulated on SLCs in both RA and OA, and CD68 was found to be an unreliable macrophage marker in OA intima.
Conclusions:
- Synovial MPs are highly activated and play a central role in RA pathogenesis.
- The recruitment of these activated MPs in RA is independent of lymphocyte infiltration.
- Understanding the immunophenotype of synovial MPs offers insights into RA pathobiology and potential therapeutic targets.
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