title: Mast cells are a source of transforming growth factor β in systemic sclerosis.
abstract: OBJECTIVE
  To describe the cellular source of transforming growth factor β (TGFβ) in the dermis of patients with systemic sclerosis (SSc).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Degranulation of skin mast cells can be an important mechanism of TGFβ secretion in SSc.
authors.affiliation: Newcastle University, Newcastle Upon Tyne, UK. Switzerland. Thomas.Huegle@unibas.ch
authors.forename: Thomas
authors.initials: T
authors.lastname: Hügle
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hogan
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: White
authors.forename: Jacob M
authors.initials: JM
authors.lastname: van Laar
mesh_terms: D000368:Aged; D001706:Biopsy; D015550:Cell Degranulation / Q000502:physiology; D022162:Cytoplasmic Vesicles / Q000378:metabolism / Q000473:pathology; D020405:Dermis / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000000981:diagnostic imaging / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D045743:Scleroderma, Diffuse / Q000378:metabolism* / Q000473:pathology; D045745:Scleroderma, Limited / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*; D014463:Ultrasonography
chemical_list: D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2