ABSTRACT
BACKGROUND: Dupuytren's disease is characterised by fibrotic nodule and cord formation in the palmar aponeurosis. The pathophysiology of the disease is still unknown, although cell stress and subsequent activation of immune mechanisms seems to be crucial. MATERIALS AND METHODS: Surgically obtained tissue and blood samples of 100 Dupuytren patients were processed by immunohistochemistry, flow cytometry, as well as immunoscope analysis. Macroscopically normal aponeurotic tissue served as control. RESULTS: Locally, microvascular alterations and massive infiltration by mononuclear cells (CD3+, CD4 > CD8, CD45RO > CD45RA, S100 protein, CD56, CD68, scarce CD19 and mast cells) forming perivascular clusters were found in DD tissue. Cytokine profiling of fibromatosis tissue-derived T-cells showed a Th1/TH17-weighted immune response. Immunoscope analysis revealed a restricted T-cell receptor α/ß repertoire pointing to an (auto)antigen-driven process. CONCLUSION: The striking accumulation of immune cells, expression of leukocyte adhesion molecules, as well as pro-inflammatory and pro-fibrotic cytokines near markedly narrowed vessels supports the theory that the abnormal proliferation of fibroblasts and production of extracellular matrix proteins in DD seems to be related to immune-mediated microvascular damage. The restricted T-cell receptor repertoire of intra-lesional T-cells points to an antigen-driven process. T-cells seem to play an important role in the development of Dupuytren's disease.
Subject(s)
Dupuytren Contracture/immunology , Dupuytren Contracture/metabolism , Adult , Aged , Aged, 80 and over , Amine Oxidase (Copper-Containing)/metabolism , Cell Adhesion Molecules/metabolism , Chaperonin 60/metabolism , Cytokines/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Female , Flow Cytometry , Forkhead Transcription Factors/metabolism , HLA-DR Antigens/metabolism , Humans , Immunohistochemistry , Leukocytes, Mononuclear/metabolism , Male , Mast Cells/metabolism , Middle Aged , Th1 Cells/metabolism , Th17 Cells/metabolism , Young AdultABSTRACT
To address the question of a possible effect of magnetic fields (MF) at 50 Hz on living systems, gene expression analyses were performed on human primary vascular endothelial cells exposed to MF of various intensities compared to control cells. Exposure protocols included continuous exposure at a single intensity (10 and 700 microT), intermittent exposure at a single intensity (700 microT), and continuous exposure to a variable-intensity field (10-30 microT). The transcriptional response of the cells was investigated using oligonucleotide microarrays containing up to 30 000 unique features. Although in individual experiments genes were identified where the expression appeared to be affected by exposure to MF, none of these genes were regulated in the same manner in subsequent repetition experiments. This is the first report of a transcriptome-wide analysis of the effects of MF exposure on human cells. The lack of a reproducible effect of MF on the expression of any genes in our investigation adds further weight to the evidence that 50-Hz MF are not capable of interacting with biological systems and thus do not represent an endothelial stress factor.
