ABSTRACT
This chapter aims to determine the amyloid-forming capability of various mutants of serum amyloid A (SAA)1.1 and SAA2.2 in cell culture systems and thereby identify specific residues in SAA1.1 that correlate not only with fibrillogenesis but also with production of stable amyloid deposits. SAA1.1 is highly amyloidogenic in mice and in macrophage and fibroblast cultures. Purified mutant SAAs were tested for amyloid-forming capacity in cell culture models. SAA2.2 proteins mutated to match SAA1.1 at one or more positions were tested for gain of amyloid-forming capacity. While the vast majority of SAA mutant proteins did not produce amyloid, many showed deposition in cell cultures. These extracellular deposits, which did not stain with Congo red, were cleared from macrophage cultures over time, indicating susceptibility to proteolysis not demonstrated by SAA1.1-derived amyloid. Similar resorption of non-amyloid deposits was not observed in fibroblast cultures.
