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.
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.
Okawa-Takatsuji
M
M
Division of Clinical Immunology, Clinical Research Institute, Tokyo, Japan.
Aotsuka
S
S
Fujinami
M
M
Uwatoko
S
S
Kinoshita
M
M
Sumiya
M
M
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000494:pharmacology*; D001324:Autoantigens / Q000276:immunology* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D003240:Connective Tissue Diseases / Q000276:immunology*; D004247:DNA / Q000276:immunology; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000276:immunology; D011651:Pulmonary Artery / Q000276:immunology*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology; D015854:Up-Regulation
D001323:Autoantibodies; D001324:Autoantigens; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007375:Interleukin-1; D017412:Ribonucleoprotein, U1 Small Nuclear; D018799:Intercellular Adhesion Molecule-1; D004247:DNA