Mercuric chloride-induced vasculitis in the Brown Norway rat: alpha beta T cell-dependent and -independent phases: role of the mast cell.
Mercuric chloride induces a necrotizing vasculitis in the Brown Norway (BN) rat. This occurs in two phases, between 1 and 5 days (early) and between 12 and 20 days (late) after initiation of HgCl2. One outbred and four inbred rat strains were found to be susceptible to early vasculitis, but only the BN strain developed late vasculitis. In the BN strain, treatment with the mAb R73 (anti-alpha beta TCR) inhibited T cell function, completely prevented the late vasculitis, but had no effect against early vasculitis, indicating that early and late vasculitis is controlled by different genetic and cellular mechanisms. The role of the mast cell in the alpha beta T cell-independent early phase was studied. Serum concentrations of rat mast cell protease II rose following HgCl2 treatment, indicating mast cell degranulation. The reagents Doxantrazole and the mAb G63, which suppress mast cell secretory responses, also prevented the rise in rat mast cell protease II and significantly reduced the early vasculitis. The demonstration of an alpha beta T cell-dependent phase supports previous experimental data that T cells play an important role in the pathogenesis of vasculitis. The presence of an earlier alpha beta T cell-independent phase is a unique observation. The data support a role for the mast cell in the early vasculitis.
Kiely
P D
PD
Division of Renal Medicine, St. George's Hospital Medical School, London, United Kingdom.
Pecht
I
I
Oliveira
D B
DB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D053818:Chymases; D004198:Disease Susceptibility; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008407:Mast Cells / Q000201:enzymology / Q000276:immunology*; D008627:Mercuric Chloride; D051381:Rats; D011914:Rats, Inbred BN / Q000235:genetics / Q000276:immunology*; D017208:Rats, Wistar; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D012697:Serine Endopeptidases / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D013997:Time Factors; D014657:Vasculitis / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016693:Receptors, Antigen, T-Cell, alpha-beta; D008627:Mercuric Chloride; D012697:Serine Endopeptidases; D053818:Chymases