Impaired degradation of serum amyloid A (SAA) protein by cytokine-stimulated monocytes

Clin Exp Immunol. 2001 Mar;123(3):408-11. doi: 10.1046/j.1365-2249.2001.01472.x.

Abstract

Secondary amyloidosis (AA amyloidosis) is a systemic disease characterized by the extracellular tissue deposition of insoluble amyloid A (AA) protein. Aberrant metabolism of serum amyloid A (SAA) by macrophages is only one of many putative mechanisms which may be important in AA amyloidogenesis. In this study, we investigated the effects of cytokines on human monocyte-mediated SAA proteolysis. Human peripheral blood mononuclear cells (PBMC) or CD14(+) monocytes were cultured with SAA, and the culture supernatants were then subjected to anti-SAA immunoblot. CD14(+) monocytes degraded SAA completely. Whereas, when CD14(+) monocytes were pretreated with IL-1 beta or IFN-gamma, increasing amounts of SAA-related derivatives were detected in culture supernatants. These findings suggest that activation of monocytes by IL-1 beta or IFN-gamma hampers the proteolysis of a precursor protein and leads to a partial degradation of SAA. This down-regulated proteolysis of SAA protein by cytokine-stimulated monocytes may play a role in the mechanism of AA amyloid formation as well as its removal.

MeSH terms

  • Amyloidosis / etiology
  • Apolipoproteins / metabolism*
  • Cytokines / pharmacology*
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Lipopolysaccharide Receptors
  • Monocytes / metabolism*
  • Serum Amyloid A Protein / metabolism*

Substances

  • Apolipoproteins
  • Cytokines
  • Interleukin-1
  • Lipopolysaccharide Receptors
  • Serum Amyloid A Protein
  • Interferon-gamma