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Abstract
Objective. Synovial fibroblasts share a number of phenotype markers with fibroblasts derived from bone marrow. In this study we investigated the role of matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and skin) to test the hypothesis that synovial fibroblasts share similarities with bone marrow-derived fibroblasts in terms of their ability to support survival of T cells and neutrophils. Methods. Matched synovial, bone marrow, and skin fibroblasts were established from 8 different patients with rheumatoid arthritis who were undergoing knee or hip surgery. Resting or activated fibroblasts were cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte survival, apoptosis, and proliferation were measured. Results. Fibroblasts derived from all 3 sites supported increased survival of CD4 T cells, mediated principally by interferon-beta. However, synovial and bone marrow fibroblasts shared an enhanced site-specific ability to maintain CD4 T cell survival in the absence of proliferation, an effect that was independent of fibroblast activation or proliferation but required direct T cell-fibroblast cell contact. In contrast, fibroblast-mediated neutrophil survival was less efficient, being independent of the site of origin of the fibroblast but dependent on prior fibroblast activation, and mediated solely by soluble factors, principally granulocyte-macrophage colony-stimulating factor. Conclusion. These results suggest an important functional role for fibroblasts in the differential accumulation of leukocyte subsets in a variety of tissue microenvironments. The findings also provide a potential explanation for site-specific differences in the pattern of T cell and neutrophil accumulation observed in chronic inflammatory diseases.
Original language | English |
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Pages (from-to) | 2096-2108 |
Number of pages | 13 |
Journal | Arthritis & Rheumatism |
Volume | 54 |
Issue number | 7 |
Early online date | 26 Jun 2006 |
DOIs | |
Publication status | Published - 1 Jul 2006 |
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Dive into the research topics of 'Differential leucocyte subset survival mediated by synovial, bone marrow and skin fibroblasts in rheumatoid arthritis: site specific versus activation dependent survival of T cells and neutrophils'. Together they form a unique fingerprint.Projects
- 1 Finished
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The Role of Fibroblasts in the Regulation of Leucocyte Retention in Chronic Inflammation
Buckley, C.
1/10/01 → 30/09/06
Project: Research Councils