Up-regulation of intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1) and class II MHC molecules on pulmonary artery endothelial cells by antibodies against U1-ribonucleoprotein

Clin Exp Immunol. 1999 Apr;116(1):174-80. doi: 10.1046/j.1365-2249.1999.00864.x.

Abstract

In order to elucidate the pathogenic role(s) of autoantibodies in connective tissue disease (CTD), we examined whether autoantibodies against U1-ribonucleoprotein (RNP) and double-stranded (ds) DNA can up-regulate ICAM-1, ELAM-1 and class I and II MHC molecule expression on pulmonary artery endothelial cells (HPAEC). ICAM-1, ELAM-1 and class II MHC molecule expression on HPAEC cultured in the presence of anti-U1-RNP-containing and anti-dsDNA-containing IgG from CTD patients was up-regulated significantly in comparison with that on HPAEC cultured with IgG from normal healthy volunteers. Affinity chromatographic enrichment and depletion of the anti-U1-RNP antibody content of anti-U1-RNP-containing IgG confirmed that the anti-U1-RNP antibody did up-regulate ICAM-1, ELAM-1 and class II MHC molecule expression. The finding that an IgG F(ab')2-purified anti-U1-RNP antibody also up-regulated expression of these molecules may indicate that mechanisms other than Fc receptor-mediated stimulation are involved. These in vitro findings suggest that autoantibodies against U1-RNP and dsDNA play important roles in the immunopathological processes leading to the proliferative pulmonary arterial vasculopathy observed in CTD patients with pulmonary hypertension by up-regulating adhesion and class II MHC molecule expression on endothelial cells.

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / pharmacology*
  • Autoantigens / immunology*
  • Autoantigens / pharmacology
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules / biosynthesis*
  • Connective Tissue Diseases / immunology*
  • DNA / immunology
  • E-Selectin / biosynthesis
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / immunology*
  • Female
  • Histocompatibility Antigens Class II / biosynthesis*
  • Humans
  • Immunoglobulin G / pharmacology
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-1 / pharmacology
  • Male
  • Middle Aged
  • Mixed Connective Tissue Disease / immunology
  • Pulmonary Artery / immunology*
  • Ribonucleoprotein, U1 Small Nuclear / immunology
  • Scleroderma, Systemic / immunology
  • Sjogren's Syndrome / immunology
  • Up-Regulation

Substances

  • Autoantibodies
  • Autoantigens
  • Cell Adhesion Molecules
  • E-Selectin
  • Histocompatibility Antigens Class II
  • Immunoglobulin G
  • Interleukin-1
  • Ribonucleoprotein, U1 Small Nuclear
  • Intercellular Adhesion Molecule-1
  • DNA