Acute-phase serum amyloid A production by rheumatoid arthritis synovial tissue

SAA is the circulating precursor of amyloid A protein, the fibrillar component of amyloid deposits [ 1 , 2 ]. Four human SAA genes have been described. Two genes ( SAA1 and SAA2 ) encode A-SAA and are coordinately induced in response to inflammation. SAA1 and SAA2 are 95% homologous in both coding and noncoding regions. SAA3 is a pseudogene. SAA4 encodes constitutive SAA and is minimally inducible. A-SAA increases dramatically during acute inflammation and may reach levels that are 1000-fold greater than normal [ 3 , 4 ]. A-SAA is mainly synthesized in the liver [ 5 ], but extrahepatic production has been demonstrated in many species, including in humans. A-SAA mRNA is expressed in RA synoviocytes [ 6 ] and in monocyte/macrophage cell lines such as THP-1 cells (Human monocyte cell line American Type Culture Collection Tumor Immunology bank 17 - ATCC TIB) [ 7 ], in endothelial cells and smooth muscle cells of atherosclerotic lesions [ 8 ]. A-SAA has also been localized to a wide range of histologically normal tissues, including breast, stomach, intestine, pancreas, kidney, lung, tonsil, thyroid, pituitary, placenta, skin and brain [ 9 ].