Early vasculitis in the mercuric chloride induced Brown Norway rat model is neutrophil independent.
In the Brown Norway rat, mercuric chloride (HgCl2) induces an autoimmune syndrome characterized by necrotizing vasculitis, predominantly affecting the caecum, and a polyclonal B-cell response. The time course of vasculitis is biphasic, with an alphabeta T-cell independent phase occurring within 24 h, and a T-cell and neutrophil dependent phase, maximal at two weeks. The pathogenesis of the early phase of vasculitis is unclear, and this study aims to examine the role of neutrophils. Rat neutrophils were depleted using cyclophosphamide. RP3, an antirat neutrophil monoclonal antibody, inhibited neutrophil leucocytosis but did not deplete neutrophils. Vasculitis was induced by subcutaneous HgCl2 injection. Serial measurements of peripheral blood leucocyte count were made. Rats were killed after 24 or 72 h. The macroscopic appearance of the caecum was scored by an experienced observer, and samples taken for histological examination. Caecums were excised and myeloperoxidase, a marker enzyme for neutrophil infiltration, assayed. Cyclophosphamide induced marked neutropaenia whereas RP3 inhibited the neutrophilia observed after HgCl2 injection. Vasculitis was present in both treated and control animals, with no significant differences in macroscopic or microscopic scores between the groups. Tissue myeloperoxidase activity was low in all animals and did not differ significantly between groups. The data do not support a role for neutrophils in the initial pathogenesis of vasculitis in this model.
Harris
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Division of Renal Medicine, St. George's Hospital Medical School, London, UK.
Turner
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Oliveira
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D000818:Animals; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D002429:Cecal Diseases / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007958:Leukocyte Count; D008297:Male; D008627:Mercuric Chloride; D009504:Neutrophils / Q000276:immunology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000201:enzymology / Q000276:immunology* / Q000473:pathology
D008627:Mercuric Chloride; D009195:Peroxidase