Mast cells are a source of transforming growth factor β in systemic sclerosis

Abstract

To describe the cellular source of transforming growth factor β (TGFβ) in the dermis of patients with systemic sclerosis (SSc). We performed electron microscopy (EM) with immunogold labeling on skin biopsy specimens from 7 patients with SSc and 3 healthy control subjects. For TGFβ quantification, the numbers of gold particles per square micron were calculated. The origin of mast cells was confirmed and quantified by toluidine blue staining and light microscopy. Degranulation was assessed on toluidine blue-stained sections and on EM images. In all patients, active TGFβ was observed uniquely in mast cell vesicles, some of which were released into the extracellular space. Patients with progressive SSc and a more recent onset of non-Raynaud's phenomenon symptoms had higher numbers of mast cells and gold particles per mast cell. Mast cells from healthy control subjects also contained active TGFβ but, in contrast to SSc samples, showed a resting character with no or low-level degranulation and uniformly dense osmiophilic vesicles. Degranulation of skin mast cells can be an important mechanism of TGFβ secretion in SSc.