Differential expression of the amyloid SAA 3 gene in liver and peritoneal macrophages of mice undergoing dissimilar inflammatory episodes.
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.
Rokita
H
H
Thorndike Memorial Laboratory, Department of Medicine, Boston City Hospital, MA.
Shirahama
T
T
Cohen
A S
AS
Meek
R L
RL
Benditt
E P
EP
Sipe
J D
JD
D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D005796:Genes; D007249:Inflammation; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D010529:Peritoneal Cavity / Q000473:pathology; D000685:Serum Amyloid A Protein / Q000096:biosynthesis* / Q000235:genetics
D000685:Serum Amyloid A Protein