Anti-endothelial cell IgG fractions from systemic lupus erythematosus patients bind to human endothelial cells and induce a pro-adhesive and a pro-inflammatory phenotype in vitro.
Affinity purified immunoglobulin G (IgG) fractions from systemic lupus erythematosus (SLE) patients positive for anti-endothelial cell antibodies (AECA) bind human umbilical vein endothelial cell (HUVEC) monolayers. In vitro incubation of serial protein concentrations of SLE AECA IgG induces a dose-dependent endothelial activation: i) increase of functional adhesion of the monocytic cell line U937; ii) upregulation of E-Selectin, ICAM-1, VCAM-1 expression evaluated by a cell solid-phase enzyme linked immunoassay; and iii) increased secretion of interleukin (IL)-6 in the culture supernatants. Control experiments carried out with HUVEC monolayers incubated with IgG fractions from normal healthy controls or from AECA negative SLE sera do not affect at all endothelial adhesion molecule expression or pro-inflammatory cytokine secretion. The AECA IgG effects are not related to both anti-phospholipid or anti-DNA activities. Taken together the findings suggest that these autoantibodies might be important in recruiting and in activating mononuclear leukocytes responsible for vessel wall infiltration and raise the possibility that AECA might display a pathogenic role in SLE vessel damage.
Del Papa
N
N
Department of Internal Medicine, Spedali Civili, Brescia, Italy.
Raschi
E
E
Moroni
G
G
Panzeri
P
P
Borghi
M O
MO
Ponticelli
C
C
Tincani
A
A
Balestrieri
G
G
Meroni
P L
PL
D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D002448:Cell Adhesion / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis / Q000276:immunology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020298:U937 Cells
D001323:Autoantibodies; D019040:E-Selectin; D007074:Immunoglobulin G; D015850:Interleukin-6