Lack of graft-versus-host-like pathology in mercury-induced autoimmunity of Brown Norway rats.
The repeated administration of mercury to Brown Norway (BN) rats induces the production of autoantibodies to laminin 1 and other autoantigens, accompanied by renal deposition of immunoglobulins and a membranous glomerulonephropathy. A graft-versus-host-like (GVHL) syndrome, characterized by widespread necrotizing leukocytoclastic vasculitis of the bowel, skin, and other tissues, has also been observed after mercury treatment of BN rats. These findings have suggested that the autoimmunity caused by the administration of mercury to BN rats may result as a xenobiotic-induced GVHL effect under the control of OX22+ T lymphocytes. However, previous studies of mercury-induced autoimmunity have never reported any evidence of GVHL lesions. Therefore, we have carefully examined various tissues from a large group of BN rats injected with HgCl(2) to identify possible areas of inflammatory reactions that may have been unnoticed in previous investigations. In addition, we have determined by flow cytometry whether exposure to mercury results in percentage and numerical alterations of OX22+ or other lymphocyte subpopulations in lymphoid organs of HgCl(2)-treated BN rats. The present article confirms that mercury induces autoimmune responses to laminin 1 but does not corroborate the hypothesis of a GVHL syndrome regulated by OX22+ lymphocytes. First, changes in OX22+ cells during treatment with HgCl(2) were infrequent and had no significant correlation with the kinetics of autoimmune responses to laminin 1. Second, we detected no GVHL lesions in skin and intestine of mercury-treated BN rats.
Department of Pathology, University of Connecticut School of Medicine, Farmington, CT 06030, USA. rpelletier@nsol.uchc.edu
P E
PE
Bigazzi
L L
LL
Kosuda
M O
MO
Hannigan
B
B
Whalen
D L
DL
Greiner
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D015433:Glomerulonephritis, Membranous / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007797:Laminin / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D008627:Mercuric Chloride / Q000276:immunology / Q000633:toxicity*; D051381:Rats; D011914:Rats, Inbred BN; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology
D001323:Autoantibodies; D007797:Laminin; C121346:laminin 1; D008627:Mercuric Chloride