Graves' immunoglobulins and cytokines stimulate the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured Graves' orbital fibroblasts

Eur J Clin Invest. 1992 Aug;22(8):529-37. doi: 10.1111/j.1365-2362.1992.tb01501.x.


Intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-asociated antigen-1 (LFA-1) are cell surface adhesion receptors that bind to one another and promote a variety of effector/target cell interactions in tissues affected by inflammatory or immune processes. Local infiltration of the thyroid gland and the retro-ocular space by mononuclear cells is a hallmark of Graves' disease and Graves' ophthalmopathy (GO). Thus, we studied the role of these adhesion receptors in the interaction of inflammatory cells with retro-ocular fibroblasts (OF) derived from patients undergoing transantral decompression for severe GO, and from normal individuals. Confluent OF-monolayers were incubated with various cytokines or protein-A affinity-purified IgGs prepared from sera of patients with severe GO, Hashimoto's thyroiditis (HT), rheumatoid arthritis (RA) and normal individuals. As determined by immunocytochemistry and immunoprecipitation using a monoclonal anti-ICAM-1 antibody, interleukin-1-alpha (IL-1a), tumour necrosis factor-alpha (TNFa) and interferon-gamma (IFNg) strongly enhanced surface expression of ICAM-1 in both GO- and normal OF. By contrast, Graves' IgGs stimulated ICAM-1 expression only in GO-, but not in normal OF. No effect was observed in either cell type with interleukin-2, transforming growth factor-beta, or IgGs from patients with HT, RA and normal individuals. Using phorbol ester-activated, 51Cr-labelled peripheral blood mononuclear cells (PBMCs) in a cell adhesion assay, we demonstrated potent adhesive activity of ICAM-1 in GO-OF pretreated with IL-1a, TNFa, IFNg or Graves' IgGs, while all other compounds did not affect PBMC adhesion to GO-OF.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / biosynthesis*
  • Cell Adhesion Molecules / biosynthesis*
  • Cells, Cultured
  • Connective Tissue / drug effects
  • Connective Tissue / immunology
  • Connective Tissue / physiopathology*
  • Cytokines / pharmacology*
  • Eye
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Fibroblasts / physiology
  • Fluorescent Antibody Technique
  • Graves Disease / immunology*
  • Humans
  • Immunoglobulins / isolation & purification
  • Immunoglobulins / physiology*
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Interleukin-2 / pharmacology
  • Lymphotoxin-alpha / pharmacology
  • Methionine / metabolism
  • Recombinant Proteins / pharmacology
  • Sulfur Radioisotopes
  • Tumor Necrosis Factor-alpha / pharmacology


  • Antigens, CD
  • Cell Adhesion Molecules
  • Cytokines
  • Immunoglobulins
  • Interleukin-1
  • Interleukin-2
  • Lymphotoxin-alpha
  • Recombinant Proteins
  • Sulfur Radioisotopes
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma
  • Methionine