Animal models of systemic vasculitis.
Necrotizing leucocytoclastic vasculitis is the histopathological hallmark of the small vessel systemic vasculitides (SV), a group of human diseases commonly associated with anti-neutrophil cytoplasm autoantibodies (ANCA). Necrotizing vasculitis is seen in a number of experimental systems, but none of these provide an ideal animal model for human SV. Vasculitis occurs in serum sickness reactions; in murine models of systemic lupus erythematosus; in association with infection, particularly chronic viral infections; and after treatment with certain drugs or inflammatory mediators. 'Spontaneous' vasculitis has been reported in specific mouse strains, especially with ageing, and in some larger species. The size of vessel involved and the type of inflammatory cells predominating are variable in these experimental situations, and none of these models feature antibodies analogous to ANCA. We have recently reported that Brown Norway rats treated with mercuric chloride (HgCl2) develop necrotizing leucocytoclastic vasculitis, especially in the gut, and also develop antibodies to myeloperoxidase (MPO) which recognize similar determinants on MPO to those bound by a subset of ANCA. Transfer of serum from HgCl2-treated rats to naive animals does not induce tissue injury. Preliminary experiments using pooled immunoglobulin or an anti-CD4 monoclonal antibody did not show useful therapeutic benefit from these treatments. HgCl2-induced vasculitis has weaknesses as an animal model of human SV, but is the only experimental model in which anti-MPO autoantibodies have so far been demonstrated, and therefore may be of particular relevance to ANCA-associated SV.
Department of Medicine, University of Cambridge, UK.
P W
PW
Mathieson
F J
FJ
Qasim
V L
VL
Esnault
D B
DB
Oliveira
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy; D001485:Basement Membrane / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology; D004195:Disease Models, Animal; D004285:Dogs; D004342:Drug Hypersensitivity / Q000276:immunology; D006736:Horses; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007167:Immunotherapy; D007239:Infections / Q000150:complications; D007678:Kidney Glomerulus / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology; D008627:Mercuric Chloride / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008809:Mice, Inbred C3H / Q000276:immunology; D008817:Mice, Mutant Strains / Q000276:immunology; D009336:Necrosis; D009504:Neutrophils / Q000276:immunology / Q000648:ultrastructure; D009195:Peroxidase / Q000276:immunology; D010865:Pilot Projects; D011817:Rabbits; D051381:Rats; D011914:Rats, Inbred BN / Q000276:immunology; D012713:Serum Sickness / Q000150:complications; D014657:Vasculitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy
D019268:Antibodies, Antineutrophil Cytoplasmic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D016756:Immunoglobulins, Intravenous; D008627:Mercuric Chloride; D009195:Peroxidase