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 in | Arthritis and rheumatism Vol. 63; no. 3; pp. 795 - 799 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.03.2011
Wiley |
Subjects | |
Online Access | Get full text |
ISSN | 0004-3591 1529-0131 1529-0131 |
DOI | 10.1002/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. |
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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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Keywords | Immunopathology Connective tissue disease Skin disease Transforming growth factor β Systemic disease Rheumatology Autoimmune disease Mast cell Scleroderma |
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References | 1990; 86 1990; 33 1997; 62 1993; 28 2003; 70 1994; 180 1995; 22 1999; 21 2001; 28 1998; 110 2001; 13 2003; 22 1993; 122 1990; 94 Satomura (10.1002/art.30190-BIB14|cit14) 2003; 70 Desmouliere (10.1002/art.30190-BIB3|cit3) 1993; 122 Gruschwitz (10.1002/art.30190-BIB5|cit5) 1990; 94 Gordon (10.1002/art.30190-BIB9|cit9) 1994; 180 Seibold (10.1002/art.30190-BIB10|cit10) 1990; 33 Brito (10.1002/art.30190-BIB13|cit13) 1997; 62 Clements (10.1002/art.30190-BIB12|cit12) 1995; 22 Denton (10.1002/art.30190-BIB1|cit1) 2001; 13 Ozbilgin (10.1002/art.30190-BIB4|cit4) 2003; 22 LeRoy (10.1002/art.30190-BIB11|cit11) 2001; 28 Kawakami (10.1002/art.30190-BIB2|cit2) 1998; 110 Querfeld (10.1002/art.30190-BIB7|cit7) 1999; 21 Galli (10.1002/art.30190-BIB8|cit8) 1993; 28 Kulozik (10.1002/art.30190-BIB6|cit6) 1990; 86 |
References_xml | – volume: 110 start-page: 47 year: 1998 end-page: 51 article-title: Increased expression of TGF‐β receptors by scleroderma fibroblasts: evidence for contribution of autocrine TGF‐β signaling to scleroderma phenotype publication-title: J Invest Derm – volume: 122 start-page: 103 year: 1993 end-page: 11 article-title: Transforming growth factor‐β1 induces α‐smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts publication-title: J Cell Biol – volume: 70 start-page: 490 year: 2003 end-page: 5 article-title: Increased chymase in livers with autoimmune disease: colocalization with fibrosis publication-title: J Nippon Med Sch – volume: 21 start-page: 13 year: 1999 end-page: 22 article-title: Expression of TGF‐β1, ‐β2 and ‐β3 in localized and systemic scleroderma publication-title: J Dermatol Sci – volume: 33 start-page: 1702 year: 1990 end-page: 9 article-title: Dermal mast cell degranulation in systemic sclerosis publication-title: Arthritis Rheum – volume: 13 start-page: 505 year: 2001 end-page: 11 article-title: Transforming growth factor‐β and connective tissue growth factor: key cytokines in scleroderma pathogenesis publication-title: Curr Opin Rheumatol – volume: 86 start-page: 917 year: 1990 end-page: 22 article-title: Co‐localization of transforming growth factor β2 with α1(I) procollagen mRNA in tissue sections of patients with systemic sclerosis publication-title: J Clin Invest – volume: 180 start-page: 2027 year: 1994 end-page: 37 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 – volume: 22 start-page: 1281 year: 1995 end-page: 5 article-title: Inter and intraobserver variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis publication-title: J Rheumatol – volume: 62 start-page: 389 year: 1997 end-page: 96 article-title: Liver granulomas in schistosomiasis: mast cell‐dependent induction of SCF expression in hepatic stellate cells is mediated by TNF‐α publication-title: J Leukoc Biol – volume: 94 start-page: 197 year: 1990 end-page: 203 article-title: Transcription and expression of transforming growth factor type β in the skin of progressive systemic sclerosis: a mediator of fibrosis? 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publication-title: J Invest Derm doi: 10.1111/1523-1747.ep12874503 – volume: 33 start-page: 1702 year: 1990 ident: 10.1002/art.30190-BIB10|cit10 article-title: Dermal mast cell degranulation in systemic sclerosis publication-title: Arthritis Rheum 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 – volume: 13 start-page: 505 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 |
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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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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 |
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