Murine tissue macrophages synthesize and secrete amyloid proteins different to amyloid A (AA).

We recently demonstrated that serum amyloid A (SAA) gene expression can be induced in extrahepatic sites with exception of the brain. Furthermore we demonstrated that tissue macrophages express SAA-gene constitutively and that SAA-gene expression can be increased by endotoxin. Until now the protein corresponding to the SAA-specific mRNA contained in macrophages has not been identified. We compared proteins precipitated from endogenously labelled samples by three antisera against amyloid A (AA) raised in different laboratories. Radiolabelled samples were derived from murine hepatocyte cultures, from cell-free translation of acute phase liver RNA or hepatocytes RNA and from peritoneal macrophages as well as Kupffer cells. All three antisera recognize a protein of 12.5 kDa Mr produced by hepatocytes (SAA), and a major protein of 14.3 kDa Mr contained in the cell-free translation products; this is the precursor of the mature SAA as demonstrated by cleavage experiments with canine pancreas microsomal enzymes. The antisera also recognize two proteins--a major one of 14.5 kDa Mr and a second of 12.5 kDa Mr contained in the supernatants and cell lysates of liver and peritoneal macrophages. New antisera raised against the two proteins do not recognize any protein, either of hepatocyte or of cell-free translation samples; they specifically precipitate two proteins from macrophage samples with the same molecular mass as that of the proteins precipitated by the anti SAA antisera. Murine acute phase sera do not react with the new antisera. However, amyloid deposits of amyloidotic mice specifically react with the new antisera. We describe two new components of murine amyloid produced by tissue macrophages.