Graves' immunoglobulins and cytokines stimulate the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured Graves' orbital fibroblasts.
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)
Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905.
A E
AE
Heufelder
R S
RS
Bahn
D015703:Antigens, CD / Q000096:biosynthesis*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D003238:Connective Tissue / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology*; D016207:Cytokines / Q000494:pharmacology*; D005123:Eye; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006111:Graves Disease / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000302:isolation & purification / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008715:Methionine / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013462:Sulfur Radioisotopes; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007136:Immunoglobulins; D007375:Interleukin-1; D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D008715:Methionine