Synthesis, metabolism andfibrillogenesis of serum amyloid A bymonocytes or macrophages

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Serum amyloid A (SAA) is a precursor of AA proteins, the main constituent of reactive amyloid deposits. Macrophages play a central role in AA fibrillogenesis and the cells can produce SAA. In this study, using a monocytic leukemia cell line THP-1 as a model of macrophages, several features in SAA synthesis by monocytes/macrophages were examined. The cells secrete SAA mainly by IL-1 and glucocorticoid is critical for SAA production. Indeed, in the presence of glucocorticoid, THP-1 can produce SAA under the culture condition using common media containing calf serum. These features are quite different from those of hepatocytes, the main producer of SAA. These results imply that SAA may be produced by macrophages, and possibly other non-hepatic tissues under the physiological conditions although the amount is not comparable with that from the liver at inflammation. The possibility that macrophages utilize self-produced SAA in fibril formation when glucocorticoid is used therapeutically cannot be ruled out. Next, whether or not THP-1 cells can make amyloid fibrils when SAA proteins are added to its culture media was assessed. Several conditions were attempted, but failed to yield congo red positive materials. THP-1 cells were highly aggregated by the addition of SAA, it may represent the feature of SAA as chemoattractant. For fibrils formation, further alteration of experimental conditions may be necessary.