Natural and disease associated anti-myeloperoxidase (MPO) autoantibodies.
Myeloperoxidase (MPO) is a cationic protein present in primary azurophilic granules of neutrophils and monocytes. MPO produces a highly deleterious reactive oxygen species, the hypochlorous acid (HOCl), using hydrogen peroxide (H(2)O(2)) and chloride ions as substrate. Anti-MPO antibodies (Abs) are present in 70% of the cases in patients with microscopic polyangiitis (MPA), a small-sized vessel vasculitis. Anti-MPO Abs from patients with MPA can trigger the release of MPO by neutrophils and monocytes. Anti-MPO Abs can activate MPO to generate an oxidative stress deleterious for the endothelium. Thus, we recently demonstrated that MPA sera with anti-MPO Abs activated MPO in vitro, and generated hypochlorous acid, whereas sera from MPA patients with no anti-MPO Abs or healthy individuals did not. Both hypochlorous acid production and endothelial lysis were abrogated by N-acetylcysteine (NAC), an antioxidant molecule. Thus, anti-MPO Abs could play a pathogenic role in vivo by triggering an oxidative burst leading to severe endothelial damages.
Paris Descartes University, Faculty of Medicine, UPRES EA 4058, Department of Internal Medicine, Paris, France.
Philippe
P
Guilpain
Amélie
A
Servettaz
Frédéric
F
Batteux
Loïc
L
Guillevin
Luc
L
Mouthon
D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000633:toxicity; D001327:Autoimmune Diseases / Q000276:immunology*; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology; D016897:Respiratory Burst; D014657:Vasculitis / Q000276:immunology*
D001323:Autoantibodies; D009195:Peroxidase