Upregulation of adhesion molecule expression on endothelial cells by anti-DNA autoantibodies in systemic lupus erythematosus.
The mechanism of vasculopathy in systemic lupus erythematosus (SLE) remains unclear and the evidence for a direct pathogenic role of anti-double-stranded DNA antibodies (anti-dsDNA) is not strong. Our study aims to determine whether anti-dsDNA exerts any effect on the expression of adhesion molecules on endothelial cells. IgG was purified from 17 patients with SLE (median anti-dsDNA titer, 404 IU/ml) and from 9 healthy controls (median titer 16 IU/ml). Anti-dsDNA-depleted polyclonal IgG (anti-dsDNA-dep-IgG) (median anti-dsDNA titer 17 IU/ml) was prepared from sera of these patients with SLE by affinity chromatography with DNA cellulose column. Expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin on human umbilical vein endothelial cells (HUVEC) cultured with either control IgG or anti-dsDNA were compared by flow cytometry. The levels of adhesion molecules in the supernatant of cultured HUVEC were assessed by sandwich ELISA. Compared with either control IgG or anti-dsDNA-dep-IgG, HUVEC incubated with anti-dsDNA expressed a significantly higher mean fluorescence intensity of ICAM-1 and in VCAM-1 and a higher supernatant concentration of ICAM-1 and VCAM-1 but not E-selectin. At the same time, ICAM-1 mRNA was also raised with increased neutrophil adherence in HUVEC incubated with anti-dsDNA. Pretreatment of HUVEC with native DNA or histone before incubation with anti-dsDNA did not increase the expression of adhesion molecules. Our study provides in vitro evidence that anti-dsDNA could play an important pathogenic role in inducing inflammatory injury of vascular endothelium in SLE.
Lai
K N
KN
Department of Medicine, Prince of Wales Hospital, Chinese University of Hong Kong.
Leung
J C
JC
Lai
K B
KB
Wong
K C
KC
Lai
C K
CK
D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology* / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D019040:E-Selectin / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D014471:Umbilical Veins; D015854:Up-Regulation / Q000276:immunology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics
D000974:Antibodies, Antinuclear; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007074:Immunoglobulin G; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004247:DNA