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Major acute-phase reactant synthesis during chronic inflammation in amyloid-susceptible and -resistant mouse strains

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Abstract

Hepatic levels of mRNA specific for total serum amyloid A (SAA), the SAA1 and SAA2 isotypes, serum amyloid P (SAP), C-reactive protein (CRP), and fibronectin, as well as the plasma concentrations of SAA and SAP were examined in amyloid-resistant (A/J) and amyloid-susceptible (CBA/J) mice during azocaseininduced chronic inflammation. In both strains hepatic SAA and SAP mRNA levels and plasma SAA and SAP protein concentrations increased dramatically during the early stages of inflammation; this was followed by a decrease to concentrations that were maintained at levels considerably higher than background. The ratios of SAA1 and SAA2 mRNA and plasma protein were 1 ∶ 1 throughout. This indicated that there was no preferential accumulation of mRNA specifying a particular isotype and no preferential synthesis or clearance of a particular isotype during chronic inflammation and the early stages of amyloidogenesis in either strain. Similarly, hepatic SAP mRNA levels in both strains increased dramatically during the early stages of inflammation and were subsequently maintained at elevated levels. Plasma SAP concentrations increased rapidly during the first three days of the study in both A/J and CBA/J mice; however, during the later stages of inflammation, A/J plasma SAP levels decreased to a steady-state concentration that was approximately half that observed in CBA/J mice. Our results identify differences in the hepatic mRNA and plasma protein levels of the major mouse acute-phase reactants (APR) in the amyloid-resistant A/J and amyloid-susceptible CBA/J mouse strains. These findings are consistent with circulating inflammatory APR concentrations contributing, together with other factors, to the onset and pathogenesis of secondary amyloidosis.

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Authors and Affiliations

  1. Division of Immunology Children's Hospital and Department of Pediatrics Harvard Medical School, Boston, Massachusetts

    K. Zahedi, D. M. Steel & A. S. Whitehead

  2. Department of Biochemistry Boston, University School of Medicine, Boston, Massachusetts

    W. A. Gonnerman & J. D. Sipe

  3. Department of Medicine Division of Rheumatology, University of Kentucky College of Medicine, Lexington, Kentucky

    F. C. Debeer & M. C. Debeer

Authors
  1. K. Zahedi
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  2. W. A. Gonnerman
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  3. F. C. Debeer
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  4. M. C. Debeer
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  5. D. M. Steel
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  6. J. D. Sipe
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  7. A. S. Whitehead
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Zahedi, K., Gonnerman, W.A., Debeer, F.C. et al. Major acute-phase reactant synthesis during chronic inflammation in amyloid-susceptible and -resistant mouse strains. Inflammation 15, 1–14 (1991). https://doi.org/10.1007/BF00917905

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