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

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...

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Published inArthritis and rheumatism Vol. 63; no. 3; pp. 795 - 799
Main Authors Hügle, Thomas, Hogan, Vanessa, White, Kathryn E., van Laar, Jacob M.
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2011
Wiley
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ISSN0004-3591
1529-0131
1529-0131
DOI10.1002/art.30190

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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. Conclusion Degranulation of skin mast cells can be an important mechanism of TGFβ secretion in SSc.
AbstractList 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. Conclusion Degranulation of skin mast cells can be an important mechanism of TGFβ secretion in SSc.
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.
To describe the cellular source of transforming growth factor β (TGFβ) in the dermis of patients with systemic sclerosis (SSc).OBJECTIVETo 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.METHODSWe 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.RESULTSIn 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.CONCLUSIONDegranulation of skin mast cells can be an important mechanism of TGFβ secretion in SSc.
Author White, Kathryn E.
Hogan, Vanessa
Hügle, Thomas
van Laar, Jacob M.
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Issue 3
Keywords Immunopathology
Connective tissue disease
Skin disease
Transforming growth factor β
Systemic disease
Rheumatology
Autoimmune disease
Mast cell
Scleroderma
Language English
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  article-title: Dermal mast cell degranulation in systemic sclerosis
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  doi: 10.1002/art.1780331114
– volume: 180
  start-page: 2027
  year: 1994
  ident: 10.1002/art.30190-BIB9|cit9
  article-title: Promotion of mouse fibroblast collagen gene expression by mast cells stimulated via the FcϵRI: role for mast cell-derived transforming growth factor β and tumor necrosis factor α
  publication-title: J Exp Med
  doi: 10.1084/jem.180.6.2027
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  year: 2001
  ident: 10.1002/art.30190-BIB1|cit1
  article-title: Transforming growth factor-β and connective tissue growth factor: key cytokines in scleroderma pathogenesis
  publication-title: Curr Opin Rheumatol
  doi: 10.1097/00002281-200111000-00010
SSID ssj0002353
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Snippet Objective To describe the cellular source of transforming growth factor β (TGFβ) in the dermis of patients with systemic sclerosis (SSc). Methods We performed...
To describe the cellular source of transforming growth factor β (TGFβ) in the dermis of patients with systemic sclerosis (SSc). We performed electron...
To describe the cellular source of transforming growth factor β (TGFβ) in the dermis of patients with systemic sclerosis (SSc).OBJECTIVETo describe the...
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StartPage 795
SubjectTerms Aged
Biological and medical sciences
Biopsy
Cell Degranulation - physiology
Cytoplasmic Vesicles - metabolism
Cytoplasmic Vesicles - pathology
Dermis - metabolism
Dermis - pathology
Diseases of the osteoarticular system
Female
Humans
Male
Mast Cells - diagnostic imaging
Mast Cells - metabolism
Medical sciences
Microscopy, Immunoelectron
Middle Aged
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
Scleroderma, Diffuse - metabolism
Scleroderma, Diffuse - pathology
Scleroderma, Limited - metabolism
Scleroderma, Limited - pathology
Transforming Growth Factor beta1 - metabolism
Transforming Growth Factor beta2 - metabolism
Ultrasonography
Title Mast cells are a source of transforming growth factor β in systemic sclerosis
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fart.30190
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