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

A. E. heufelder, R. S. Bahn

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Abstract

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. In other studies, PBMCs or GO-OF were pre-incubated (following stimulation with cytokines or Graves' IgGs) with monoclonal antibodies against ICAM-1 or LFA-1-alpha. While PBMC-adherence was only partially inhibited by anti-ICAM-1 antibody, anti-LFA-1-alpha almost completely blocked cell attachment. In conclusion, inflammatory cytokines and Graves' IgGs are potent modulators of ICAM-1/LFA-1-mediated interactions between immunocompetent cells and GO-OF. These mechanisms likely play a role in the localization of the inflammatory infiltrate within the orbit and may affect antigen presentation and maintenance of the chronic immune process in GO.

Original languageEnglish (US)
Pages (from-to)529-537
Number of pages9
JournalEuropean Journal of Clinical Investigation
Volume22
Issue number8
StatePublished - 1992

Fingerprint

Graves Ophthalmopathy
Intercellular Adhesion Molecule-1
Fibroblasts
Immunoglobulins
Cytokines
Lymphocytes
Antigens
Blood
Blood Cells
Interleukin-1alpha
Cell Adhesion
Cell adhesion
Hashimoto Disease
Interferon-alpha
Interferon-gamma
Tumor Necrosis Factor-alpha
Cell Communication
Rheumatoid Arthritis
Staphylococcal Protein A
Phorbol Esters

Keywords

  • adhesion molecules
  • cytokines
  • fibroblast
  • Graves' IgGs
  • Graves' ophthalmopathy
  • ICAM-1
  • LFA-1

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{e337f4f7530d445cb108df7a7038dfce,
title = "Graves' immunoglobulins and cytokines stimulate the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured Graves' orbital fibroblasts",
abstract = "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. In other studies, PBMCs or GO-OF were pre-incubated (following stimulation with cytokines or Graves' IgGs) with monoclonal antibodies against ICAM-1 or LFA-1-alpha. While PBMC-adherence was only partially inhibited by anti-ICAM-1 antibody, anti-LFA-1-alpha almost completely blocked cell attachment. In conclusion, inflammatory cytokines and Graves' IgGs are potent modulators of ICAM-1/LFA-1-mediated interactions between immunocompetent cells and GO-OF. These mechanisms likely play a role in the localization of the inflammatory infiltrate within the orbit and may affect antigen presentation and maintenance of the chronic immune process in GO.",
keywords = "adhesion molecules, cytokines, fibroblast, Graves' IgGs, Graves' ophthalmopathy, ICAM-1, LFA-1",
author = "heufelder, {A. E.} and Bahn, {R. S.}",
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TY - JOUR

T1 - Graves' immunoglobulins and cytokines stimulate the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured Graves' orbital fibroblasts

AU - heufelder, A. E.

AU - Bahn, R. S.

PY - 1992

Y1 - 1992

N2 - 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. In other studies, PBMCs or GO-OF were pre-incubated (following stimulation with cytokines or Graves' IgGs) with monoclonal antibodies against ICAM-1 or LFA-1-alpha. While PBMC-adherence was only partially inhibited by anti-ICAM-1 antibody, anti-LFA-1-alpha almost completely blocked cell attachment. In conclusion, inflammatory cytokines and Graves' IgGs are potent modulators of ICAM-1/LFA-1-mediated interactions between immunocompetent cells and GO-OF. These mechanisms likely play a role in the localization of the inflammatory infiltrate within the orbit and may affect antigen presentation and maintenance of the chronic immune process in GO.

AB - 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. In other studies, PBMCs or GO-OF were pre-incubated (following stimulation with cytokines or Graves' IgGs) with monoclonal antibodies against ICAM-1 or LFA-1-alpha. While PBMC-adherence was only partially inhibited by anti-ICAM-1 antibody, anti-LFA-1-alpha almost completely blocked cell attachment. In conclusion, inflammatory cytokines and Graves' IgGs are potent modulators of ICAM-1/LFA-1-mediated interactions between immunocompetent cells and GO-OF. These mechanisms likely play a role in the localization of the inflammatory infiltrate within the orbit and may affect antigen presentation and maintenance of the chronic immune process in GO.

KW - adhesion molecules

KW - cytokines

KW - fibroblast

KW - Graves' IgGs

KW - Graves' ophthalmopathy

KW - ICAM-1

KW - LFA-1

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M3 - Article

VL - 22

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EP - 537

JO - European Journal of Clinical Investigation

JF - European Journal of Clinical Investigation

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