The three active
serum amyloid A (SAA) genes of mice, SAA 1, SAA 2, and SAA 3, are coordinately expressed in liver during acute and chronic inflammatory stimulation and experimental
amyloidosis. The genes, primarily SAA 3, are also expressed extrahepatically. The
apoprotein SAA 2 is the precursor of the
amyloid A (AA) fibril
protein that is deposited as insoluble fibrils extracellularly in spleen and other organs when
amyloidosis occurs secondarily to
inflammation. The exact cause of AA fibril formation is unknown.
Amyloid enhancing factor is a high m.w.
glycoprotein extracted from amyloidotic organs. Administration of
amyloid enhancing factor alters experimental
inflammation to bring about accelerated deposition of
amyloid A fibrils first in spleen and later in other organs. In this study, hepatic and extrahepatic expression of the SAA genes were compared during accelerated
amyloidosis relative to
inflammation uncomplicated by
amyloidosis. Differences in kinetics and pattern of SAA gene expression by resident peritoneal macrophages and liver were detected during four dissimilar inflammatory episodes. Macrophages expressed the SAA 3 gene solely, and to a greater extent in chronic than in acute
inflammation. In accelerated
amyloid induction, macrophage SAA 3 expression increased as SAA 1 and SAA 2 expression in liver decreased. However, alpha-1-acid
glycoprotein expression remained elevated throughout the course of
amyloid induction. The greatly increased expression of the SAA 3 gene by macrophages and decreased expression of the SAA 1 and SAA 2 genes in liver during
amyloidosis, suggests that altered SAA gene expression may play a pathogenetic role in experimental
amyloid deposition.