Endothelium myeloperoxidase-antimyeloperoxidase interaction in vasculitis.
Antibodies to myeloperoxidase (MPO) are found in the sera of patients with microscopic polyarteritis and idiopathic crescentic glomerulonephritis. Their pathogenicity is unknown. Studies were carried out on the binding of MPO to cultured human umbilical vein endothelial cells and the recognition of endothelium-bound MPO by antibody to MPO. Endothelial cells were cultured from human umbilical veins. The binding of MPO to endothelial cells and its inhibition by poly-D-lysine was detected using a monoclonal antibody to MPO and direct staining with APAAP and also by an enzyme-linked immunoassay (ELISA). The binding of anti-MPO antibody in the sera of patients with microscopic polyarteritis to endothelium-coated MPO was detected by ELISA. MPO bound to endothelial cells both on direct staining and ELISA and this binding was inhibited by the polycation poly-D-lysine, suggesting that it was charge mediated. Binding of anti-MPO antibody in the sera of patients with microscopic polyarteritis to endothelium-coated MPO was significantly higher than the binding of sera from normal subjects (P = 0.04), patients with idiopathic glomerulonephritis (P = 0.0005), and patients with lupus nephritis (P = 0.009). MPO binds to cultured human umbilical vein endothelium probably by a charge mechanism, and can react with anti-MPO antibodies in the sera of patients with microscopic polyarteritis as well as with a mouse monoclonal anti-MPO antibody. This binding of anti-MPO antibody to MPO fixed to the endothelial cell surface provides a mechanism by which endothelial injury and inflammation might occur in microscopic polyarteritis.
Vargunam
M
M
Renal Research Laboratory, Queen Elizabeth Hospital, Birmingham, UK.
Adu
D
D
Taylor
C M
CM
Michael
J
J
Richards
N
N
Neuberger
J
J
Thompson
R A
RA
D004730:Endothelium, Vascular / Q000201:enzymology* / Q000276:immunology; D005921:Glomerulonephritis / Q000209:etiology; D006801:Humans; D009195:Peroxidase / Q000276:immunology*; D011107:Polylysine / Q000494:pharmacology; D014657:Vasculitis / Q000201:enzymology / Q000276:immunology*
D011107:Polylysine; D009195:Peroxidase