Pneumologie 2012; 66 - A516
DOI: 10.1055/s-0032-1315523

Migratory potential of dermal fibroblasts of patients with systemic sclerosis

S Lefèvre 1, A Günther 2, E Neumann 1, U Müller-Ladner 1
  • 1Dept Internal Medicine and Rheumatology, Justus-Liebig-University Gießen, Kerckhoff Clinic, Bad Nauheim
  • 2Dept Internal Medicine, Medical Clinic II, Justus-Liebig-University Gießen, Gießen

Background: Systemic sclerosis (SSc) is characterized by fibroblast-mediated progressive skin fibrosis. Subsequent affection of internal organs leads to severe impairments of their function and lung fibrosis represents the most common cause of death in SSc. Molecular mechanisms of the spreading of SSc are largely unknown. Recent results showed the migratory potential of rheumatoid arthritis (RA) synovial fibroblasts (SFs). Based on these results, aim of this study was the analysis of migratory and adhesive properties of SSc dermal fibroblasts (DFs) and their role in SSc-spreading with focus on organ involvement.

Methods: SScDFs (in part lentivirally RFP-transduced) were injected intracutaneously into SCID mice. After 20–25 days, parts of the skin, internal organs and blood were analyzed. In addition to fluorescence analysis, immunohisto- and cytochemistry was performed with species-specific antibodies.

Multi-well culture plates were coated with Matrigel® (MG), growth factor-reduced (GFR) MG, or remained untreated, respectively. Cellular adhesion of SScDFs (n=7), RASFs (n=4), RADFs (n=5), SFs (n=1) and DFs of healthy individuals (n=6) was analyzed.

Results: SScDFs were not detected in any internal organ by fluorescence analysis or immunohistochemistry. Human SScDFs were only visible in the skin at the injection site.

Fibroblasts of SSc patients, healthy SFs and DFs showed an increased adhesion using GFR MG compared to MG (SSc: 1.22fold; healthy SFs: 1.8fold; healthy DFs: 1.3fold). By using GFR MG, a reduction of cellular adhesion of RASFs (1.4fold) and RADFs (1.06fold) was observed compared to MG.

Discussion: According to present knowledge and in comparison to results obtained from RASFs, SScDFs do not show the ability to migrate from their application site to internal organs. Adhesive properties do not differ from healthy controls. Nevertheless, SScDFs are mediators of organ fibrosis, but it seems as if there is no contribution of SScDFs to the spreading of SSc.