Impaired degradation of serum amyloid A (SAA) protein by cytokine‐stimulated monocytes
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‐1β or IFN‐γ, increasing amounts of SAA‐related derivatives were detected in culture supernatants. These findings suggest that activation of monocytes by IL‐1β or IFN‐γ 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.