autoantibodies to endothelial cell surface atp synthase, the endogenous receptor for hsp60, might play a pathogenic role in vasculatides内皮细胞表面atp合酶自身抗体,hsp60的内生受体,可能在vasculatides发挥致病作用.pdf

Autoantibodies to Endothelial Cell Surface ATP Synthase, the Endogenous Receptor for Hsp60, Might Play a Pathogenic Role in Vasculatides 1 1 ¨ 2 1,3 1,3 Jean-Eric Alard , Sophie Hillion , Loıc Guillevin , Alain Saraux , Jacques-Olivier Pers , Pierre Youinou1,3*, Christophe Jamin1,3 ´ ´ ´ 1 EA2216 ‘‘Immunology and Pathology’’ and IFR 148 ScInBioS, Universite de Brest and Universite Europeenne de Bretagne, Brest, France, 2 Department of Internal ˆ Medicine, Hopital Cochin, Paris, France, 3 Centre Hospitalier Universitaire, Brest, France Abstract Background: Heat shock protein (hsp) 60 that provides ‘‘danger signal’’ binds to the surface of resting endothelial cells (EC) but its receptor has not yet been characterized. In mitochondria, hsp60 specifically associates with adenosine triphosphate (ATP) synthase. We therefore examined the possible interaction between hsp60 and ATP synthase on EC surface. Methodology/Principal Findings: Using Far Western blot approach, co-immunoprecipitation studies and surface plasmon resonance analyses, we demonstrated that hsp60 binds to the b-subunit of ATP synthase. As a cell surface-expressed molecule, ATP synthase is potentially targeted by anti-EC-antibodies (AECAs) found in the sera of patients suffering vasculitides. Based on enzyme-linked immunosorbent assay and Western blotting techniques with F1-ATP synthase as substrate, we established the presence of anti-ATP synthase antibodies at higher frequency in patients with primary vasculitides (group I) compared with secondary v