Anti-basement membrane antibodies and antigen-antibody complexes in rabbits injected with mercuric chloride

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Abstract

New Zealand rabbits were injected three times a week with 2 mg of mercuric chloride (HgCl2) (MC) to test the hypothesis that toxic agents release autologous antigens, generating antibody response and tissue injury. After 2 weeks of injections the rabbits developed anti-basement membrane antibodies binding to renal and extrarenal basement membranes and to the peri- and endo-mysium of skeletal muscles. Glomerular histology appeared normal. Membranous glomerulonephritis developed 1–2 months later with granular subepithelial deposits containing rabbit IgG and C3. Similar deposits were present in the basement membranes of other organs. Raji cell tests for immune complexes in the sera were negative in the initial stages and positive in the late stages of the disease. Radioactive MC was found in the cytoplasm of renal tubular, intestinal, and hepatic epithelial cells but not in glomerular deposits. Renal eluates and selected sera reacted with the basement membranes and the collagen matrix in normal or collagenase-digested sections of renal or extrarenal normal rabbit tissues. This reactivity was reduced or abolished by washing tissue sections in PBS or by absorption of renal eluates with whole kidney homogenates. The findings are consistent with the hypothesis that MC induces a biphasic disease characterized first by the production of antibodies to basement membranes and the extracellular collagen matrix and subsequently by antigen-antibody complexes formed in situ and in the circulation and presumably containing soluble polysaccharide components of the collagen matrix.

References (39)

  • G. Mancini et al.

    Immunochemistry

    (1965)
  • E. Linder et al.

    Clin. Immunol. Immunopathol.

    (1972)
  • K. Schauenstein et al.

    J. Immunol. Methods

    (1976)
  • C.B. Wilson et al.

    The Kidney

  • T.W. Clarson
  • T.L. Gritzka et al.

    Amer. J. Pathol.

    (1968)
  • J. Bariéty et al.

    Amer. J. Pathol.

    (1971)
  • E. Mendema et al.

    Lancet

    (1963)
  • G.J. Beirne et al.

    Arch. Environ. Health

    (1972)
  • A.A. Roman-Franco et al.
  • M.C. Shevky et al.

    Arch. Intern. Med.

    (1923)
  • H. Puchtler et al.

    J. Histochem. Cytochem.

    (1962)
  • J.R. Hobbs et al.

    J. Pathol. Bact.

    (1963)
  • M.A. Karnowsky

    J. Cell. Biol.

    (1965)
  • G.A. Andres et al.

    J. Clin. Invest.

    (1970)
  • R.A. Lerner et al.

    J. Exp. Med.

    (1967)
  • D. Koffler et al.

    J. Exp. Med.

    (1967)
  • T.S. Edgington et al.

    Science

    (1967)
  • G.M. Williams et al.

    N. Engl. J. Med.

    (1968)
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    The results of these studies were presented to the 6th Annual Meeting of the American Society of Nephrology, Washington, D.C., November 1976.

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    Present address: Department of Pathology and Legal Medicine, University of Puerto Rico, San Juan, Puerto Rico.

    3

    Present address: University Hospital, Cardoba, Argentina.

    4

    Present address: Clinica Medica Universita, Padova, Italy.

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