Endothelial cell binding by human polyclonal anti-DNA antibodies: relationship to disease activity and endothelial functional alterations.
Polyclonal anti-dsDNA and anti-ssDNA antibodies (PoAb) that showed significant binding to human umbilical vein endothelial cells (HUVEC) were isolated from eight patients with systemic lupus erythematosus (SLE). Anti-dsDNA PoAbs from five patients and anti-ssDNA PoAbs from seven patients demonstrated enhanced binding to HUVEC during active disease, compared with PoAbs obtained from corresponding patients during remission. Reduction of the DNA content in the PoAb preparations by DNase treatment was associated with enhanced binding to HUVEC in 20 of 32 PoAbs tested, which included 75% 'active disease' PoAbs, and with reduced binding to HUVEC in three of 32 PoAbs tested, all obtained during remission. Such altered endothelial cell binding was reversed with DNA reconstitution. Binding of the remaining nine PoAbs to HUVEC was not altered by variations in their DNA content. Induced plasma membrane expression of E-selectin, but reduced expression of vascular cell adhesion molecule-1 (VCAM-1) by HUVEC, was observed following incubation of HUVEC with 'active disease' PoAbs from three and two of the eight patients, respectively. PoAbs and serum samples from two of the eight patients during active disease induced von Willebrand factor release from HUVEC, which was not observed during remission. We conclude that anti-DNA antibodies from selected patients with SLE can bind to endothelial cells. Correlation between cellular binding and disease activity suggests that such binding of anti-DNA antibodies to endothelial cells could be of pathogenic significance. Preliminary data also suggest that the expression of adhesion molecules and haemostatic factor(s) by endothelial cells may be modified following their binding by anti-DNA antibodies.
Chan
T M
TM
Department of Medicine, University of Hong Kong, Queen Mary Hospital.
Yu
P M
PM
Tsang
K L
KL
Cheng
I K
IK
D000293:Adolescent; D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D014841:von Willebrand Factor / Q000378:metabolism
D000974:Antibodies, Antinuclear; D015815:Cell Adhesion Molecules; D007074:Immunoglobulin G; D014841:von Willebrand Factor