The effect of fibroblast conditioned medium on neutrophil survival and activation

Southey, A.; O'connor, Clare M.; FitzGerald, M. X.

doi:10.1042/bst022052s

Cited by 2 publications

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“…The observation that the factor responsible for neutrophil survival was secreted by activated fibroblasts without any requirement for prior contact with neutrophils suggested to us that GM-CSF might be a possible candidate (38,39). Furthermore, GM-CSF was only produced at significant levels by fibroblasts after TNF α stimulation (Figure 6B).…”

Section: Resultsmentioning

confidence: 92%

“…Stromal cells such as fibroblasts clearly make an important contribution to neutrophil survival by secreting soluble survival factors in response to proinflammatory cytokines, regardless of the organ involved (27,38,39). The abundance of synovial fibroblasts in pannus tissue may therefore lead to significantly enhanced survival, due to soluble factors such as GM-CSF, which is found at high levels in the synovium.…”

Section: Discussionmentioning

confidence: 99%

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Differential survival of leukocyte subsets mediated by synovial, bone marrow, and skin fibroblasts: Site‐specific versus activation‐dependent survival of T cells and neutrophils

Filer¹,

Parsonage²,

Smith³

et al. 2006

Arthritis & Rheumatism

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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-␤. 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, fibroblastmediated 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 granulocytemacrophage 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.Fibroblast-like synoviocytes (FLS) interact with a wide variety of leukocyte subtypes within the synovium. In particular, direct interactions between T cells and FLS have been suggested to contribute to the persistence of synovial inflammation (1). Activated T cells modify fibroblast proliferative capacity and matrix production (2,3), while resting T cells activate FLS in vitro to produce stromelysin, interleukin-6 (IL-6), IL-8, and prostaglandin E 2 (4). A recent study demonstrated that surface-bound IL-15 and intercellular adhesion molecule 1 (ICAM-1) expressed by rheumatoid FLS in vitro induce T cell activation and production of tumor necrosis factor ␣ (TNF␣), interferon-␥ (IFN␥), and IL-17, which, in turn, feed back on FLS to induce IL-6, IL-8, and further IL-15 and ICAM-1 expression (5). A complex paracrine, proinflammatory loop is therefore gen-

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Section: Resultsmentioning

confidence: 92%