Differentiation potential of CD14+ monocytes into myofibroblasts in patients with systemic sclerosis.
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ABSTRACT: BACKGROUND: Circulating monocytes are a highly plastic and functionally heterogeneic cell type with an activated phenotype in patients with systemic sclerosis (SSc). CD14(+) monocytes have the potential to differentiate into extra-cellular matrix (ECM) producing cells, possibly participating in fibrogenesis. AIM: To study the effect of GM-CSF, IL-4 and endothelin -1 (ET-1) alone or in combination on monocyte differentiation into myofibroblasts. METHODS: CD14(+) cells were isolated from peripheral blood from 14 SSc patients and healthy controls by positive selection and incubated with different combinations of GM-CSF, IL-4 and ET-1 for 14 days. Type-1 collagen and ?-SMA were detected by Western blot, qPCR and confocal microscopy. HLA-DR, CD11c and CD14 expression was analysed by flow cytometry. A collagen gel contraction assay was performed for functional myofibroblast assessment. RESULTS: GM-CSF both induced collagen and ?-SMA expression after 14 days. ET-1 further increased GM-CSF-induced collagen expression in a dose dependent manner up to 30-fold. IL-4/GM-CSF combination leads to a more DC-like phenotype of monocytes associated with reduced collagen and ?-SMA expression compared to GM-CSF alone. Collagen and ?-SMA expression was higher in monocytes from SSc patients and monocytes were more prone to obtain a spindle form. In contrast to controls, ET-1 and IL-4 alone were sufficient to induce ?-SMA expression in monocytes from SSc patients. Despite the induction of ?-SMA expression, monocyte-derived myofibroblasts only had a moderate capability of contraction in functional analyses. CONCLUSION: SSc monocytes display increased maturation towards myofibroblasts demonstrated by their phenotype and ?-SMA expression when compared to monocytes from healthy controls, however only with minor functional contraction properties.
SUBMITTER: Binai N
PROVIDER: S-EPMC3303833 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
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