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Differentiation Potential of CD14(+) Monocytes into Myofibroblasts in Patients with Systemic Sclerosis

Lookup NU author(s): Nadine Binai, Dr Steven O'Reilly, Dr Bridget Griffiths, Professor Jaap Van Laar

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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 alpha-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 alpha-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 alpha-SMA expression compared to GM-CSF alone. Collagen and alpha-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 alpha-SMA expression in monocytes from SSc patients. Despite the induction of alpha-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 alpha-SMA expression when compared to monocytes from healthy controls, however only with minor functional contraction properties.

Publication metadata

Author(s): Binai N, O'Reilly S, Griffiths B, van Laar JM, Hugle T

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2012

Volume: 7

Issue: 3

Print publication date: 14/03/2012

Date deposited: 13/06/2012

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pone.0033508

DOI: 10.1371/journal.pone.0033508

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