Antioxidants inhibit mercuric chloride-induced early vasculitis.
In the Brown Norway (BN) rat, mercuric chloride (HgCl(2)) induces a T(h)2-dominated autoimmune syndrome which includes an early phase of mast cell-dependent vasculitis. We have shown in vitro that oxidative stress up-regulates IL-4 in mast cells and predisposes to degranulation. The aim of this study was to determine whether administration of antioxidants inhibits HgCl(2)-induced early vasculitis in vivo, and, if so, to examine whether modulation of the oxidative/antioxidative balance influences IgE and IL-4 expression by mast cells in situ. Groups of rats were given HgCl(2) + saline, HgCl(2) + N-acetyl-L-cysteine (NAC), saline + saline or saline + NAC respectively and blood was taken and animals killed 48 h later. NAC significantly reduced both HgCl2-induced early vasculitis and HgCl(2)-enhanced IgE expression on mast cells with a trend to a decrease in HgCl(2)-enhanced IL-4 expression in these cells. In addition, there was an increased rat mast cell protease (RMCP) II concentration in the serum after HgCl(2) injection and the elevated levels of RMCP II stimulated by HgCl(2) were totally abolished by the administration NAC in the HgCl(2) + NAC group. However, there was no significant change in serum total IgE concentrations between the HgCl(2) + saline group and the HgCl(2) + NAC group. The non-sulphydryl-containing antioxidants desferrioxamine and pyruvate demonstrated a similar effect in inhibiting HgCl(2)-induced early vasculitis. Our data show that administration of an antioxidant to BN rats reduces HgCl(2)-induced early vasculitis, suggesting that oxidative stress plays a role in the pathogenesis of HgCl(2)-induced early vasculitis. This finding may have implications for the understanding of the initiation in this experimental model of T(h)2 cell-driven autoimmunity and possibly of analogous human diseases.
Wu
Zhonglin
Z
Division of Renal Medicine, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. z.wu@sghms.ac.uk
Turner
David R
DR
Oliveira
David B G
DB
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D053818:Chymases; D003676:Deferoxamine / Q000737:chemistry / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008627:Mercuric Chloride / Q000037:antagonists & inhibitors; D019289:Pyruvic Acid / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D012697:Serine Endopeptidases / Q000378:metabolism; D014657:Vasculitis / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*
D000975:Antioxidants; D015847:Interleukin-4; D007073:Immunoglobulin E; D008627:Mercuric Chloride; D019289:Pyruvic Acid; D012697:Serine Endopeptidases; D053818:Chymases; D003676:Deferoxamine; D000111:Acetylcysteine