Mononuclear cells isolated from fibrotic skin lesions in avian scleroderma constitutively produce fibroblast-activating cytokines and immunoglobulin M

M. R. Duncan, B. Berman, Judith A Van de Water, R. L. Boyd, G. Wick, M. Eric Gershwin

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10 Citations (Scopus)

Abstract

University of California, Davis line 200 and 206 chickens develop an inherited autoimmune fibrotic disease associated with autoantibodies and other features similar to human scleroderma. Early in life, line 200/206 chickens develop mononuclear cell (MNC) infiltrates in the skin, followed by severe dermal fibrosis and vascular occlusions. Cultured fibroblasts derived from fibrotic skin lesions of line 200/206 chickens display an activated phenotype producing elevated quantities of collagen and glycosaminoglycan (GAG) compared to fibroblasts derived from normal chicken skin. To demonstrate a link between skin mononuclear cell infiltration and fibroblast activation, we cultured MNC isolated from developing fibrotic skin lesions, normal appearing skin, and peripheral blood of line 206 chickens for 24-72 h. Subsequent assay of MNC culture supernatants for effect on the collagen and GAG production of normal chicken skin fibroblasts demonstrated that only fibrotic lesion MNC supernatants contained significant collagen and GAG synthesis stimulatory activity. Both stimulatory activities were constitutively produced, undialyzable, heat and protease sensitive, and coeluted on gel filtration with a M(r) of 24-32 kD. Gel filtration also revealed that fibrotic lesion MNC secrete a protein >250 kD, which we have identified as immunoglobulin (Ig) M by Western blot analysis. These results demonstrate that skin infiltrating MNC secrete both fibroblast-activating cytokines and IgM and thus they likely play an important role as effector cells in the development of dermal fibrosis and autoantibodies in this avian model of scleroderma.

Original languageEnglish (US)
Pages (from-to)519-526
Number of pages8
JournalInternational Archives of Allergy and Immunology
Volume107
Issue number4
StatePublished - 1995

Fingerprint

Immunoglobulin M
Fibroblasts
Cytokines
Skin
Chickens
Glycosaminoglycans
Collagen
Autoantibodies
Gel Chromatography
Fibrosis
Autoimmune Diseases
Blood Vessels
Cultured Cells
Peptide Hydrolases
Cell Culture Techniques
Hot Temperature
Western Blotting
Phenotype

Keywords

  • Cytokine
  • Fibroblast
  • Immunoglobulin
  • Mononuclear cell
  • Scleroderma

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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title = "Mononuclear cells isolated from fibrotic skin lesions in avian scleroderma constitutively produce fibroblast-activating cytokines and immunoglobulin M",
abstract = "University of California, Davis line 200 and 206 chickens develop an inherited autoimmune fibrotic disease associated with autoantibodies and other features similar to human scleroderma. Early in life, line 200/206 chickens develop mononuclear cell (MNC) infiltrates in the skin, followed by severe dermal fibrosis and vascular occlusions. Cultured fibroblasts derived from fibrotic skin lesions of line 200/206 chickens display an activated phenotype producing elevated quantities of collagen and glycosaminoglycan (GAG) compared to fibroblasts derived from normal chicken skin. To demonstrate a link between skin mononuclear cell infiltration and fibroblast activation, we cultured MNC isolated from developing fibrotic skin lesions, normal appearing skin, and peripheral blood of line 206 chickens for 24-72 h. Subsequent assay of MNC culture supernatants for effect on the collagen and GAG production of normal chicken skin fibroblasts demonstrated that only fibrotic lesion MNC supernatants contained significant collagen and GAG synthesis stimulatory activity. Both stimulatory activities were constitutively produced, undialyzable, heat and protease sensitive, and coeluted on gel filtration with a M(r) of 24-32 kD. Gel filtration also revealed that fibrotic lesion MNC secrete a protein >250 kD, which we have identified as immunoglobulin (Ig) M by Western blot analysis. These results demonstrate that skin infiltrating MNC secrete both fibroblast-activating cytokines and IgM and thus they likely play an important role as effector cells in the development of dermal fibrosis and autoantibodies in this avian model of scleroderma.",
keywords = "Cytokine, Fibroblast, Immunoglobulin, Mononuclear cell, Scleroderma",
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T1 - Mononuclear cells isolated from fibrotic skin lesions in avian scleroderma constitutively produce fibroblast-activating cytokines and immunoglobulin M

AU - Duncan, M. R.

AU - Berman, B.

AU - Van de Water, Judith A

AU - Boyd, R. L.

AU - Wick, G.

AU - Gershwin, M. Eric

PY - 1995

Y1 - 1995

N2 - University of California, Davis line 200 and 206 chickens develop an inherited autoimmune fibrotic disease associated with autoantibodies and other features similar to human scleroderma. Early in life, line 200/206 chickens develop mononuclear cell (MNC) infiltrates in the skin, followed by severe dermal fibrosis and vascular occlusions. Cultured fibroblasts derived from fibrotic skin lesions of line 200/206 chickens display an activated phenotype producing elevated quantities of collagen and glycosaminoglycan (GAG) compared to fibroblasts derived from normal chicken skin. To demonstrate a link between skin mononuclear cell infiltration and fibroblast activation, we cultured MNC isolated from developing fibrotic skin lesions, normal appearing skin, and peripheral blood of line 206 chickens for 24-72 h. Subsequent assay of MNC culture supernatants for effect on the collagen and GAG production of normal chicken skin fibroblasts demonstrated that only fibrotic lesion MNC supernatants contained significant collagen and GAG synthesis stimulatory activity. Both stimulatory activities were constitutively produced, undialyzable, heat and protease sensitive, and coeluted on gel filtration with a M(r) of 24-32 kD. Gel filtration also revealed that fibrotic lesion MNC secrete a protein >250 kD, which we have identified as immunoglobulin (Ig) M by Western blot analysis. These results demonstrate that skin infiltrating MNC secrete both fibroblast-activating cytokines and IgM and thus they likely play an important role as effector cells in the development of dermal fibrosis and autoantibodies in this avian model of scleroderma.

AB - University of California, Davis line 200 and 206 chickens develop an inherited autoimmune fibrotic disease associated with autoantibodies and other features similar to human scleroderma. Early in life, line 200/206 chickens develop mononuclear cell (MNC) infiltrates in the skin, followed by severe dermal fibrosis and vascular occlusions. Cultured fibroblasts derived from fibrotic skin lesions of line 200/206 chickens display an activated phenotype producing elevated quantities of collagen and glycosaminoglycan (GAG) compared to fibroblasts derived from normal chicken skin. To demonstrate a link between skin mononuclear cell infiltration and fibroblast activation, we cultured MNC isolated from developing fibrotic skin lesions, normal appearing skin, and peripheral blood of line 206 chickens for 24-72 h. Subsequent assay of MNC culture supernatants for effect on the collagen and GAG production of normal chicken skin fibroblasts demonstrated that only fibrotic lesion MNC supernatants contained significant collagen and GAG synthesis stimulatory activity. Both stimulatory activities were constitutively produced, undialyzable, heat and protease sensitive, and coeluted on gel filtration with a M(r) of 24-32 kD. Gel filtration also revealed that fibrotic lesion MNC secrete a protein >250 kD, which we have identified as immunoglobulin (Ig) M by Western blot analysis. These results demonstrate that skin infiltrating MNC secrete both fibroblast-activating cytokines and IgM and thus they likely play an important role as effector cells in the development of dermal fibrosis and autoantibodies in this avian model of scleroderma.

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