Serum amyloid A

Acute-phase serum amyloid A proteins

Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of inflammation. These proteins have several roles, including the transport of cholesterol to the liver for secretion into the bile, the recruitment of immune cells to inflammatory sites, and the induction of enzymes that degrade extracellular matrix. A-SAAs are implicated in several chronic inflammatory diseases, such as amyloidosis, atherosclerosis, and rheumatoid arthritis. Three acute-phase SAA isoforms have been reported in mice, called SAA1, SAA2, and SAA3. During inflammation, SAA1 and SAA2 are expressed and induced principally in the liver, whereas SAA3 is induced in many distinct tissues. SAA1 and SAA2 genes are regulated in liver cells by the proinflammatory cytokines IL-1, IL-6, and TNF-α. Both SAA1 and SAA2 are induced up to a 1000-fold in mice under acute inflammatory conditions following exposure to bacterial lipopolysaccharide (LPS). although the third gene, SAA3, is believed to represent a pseudogene that does not generate messenger RNA or protein. Molecular weights of the human proteins are estimated at 11.7 kDa for SAA1 and 14.8 kDa for SAA4.

Serum amyloid A (SAA) is also an acute phase marker that responds rapidly. Similar to CRP, levels of acute-phase SAA increase within hours after inflammatory stimulus, and the magnitude of increase may be greater than that of CRP. Relatively trivial inflammatory stimuli can lead to SAA responses. It has been suggested that SAA levels correlate better with disease activity in early inflammatory joint disease than do ESR and CRP. Although largely produced by hepatocytes, more recent studies show that SAA is produced by adipocytes as well, and its serum concentration is associated with body mass index.

Constitutive serum amyloid A proteins

A fourth SAA (SAA4) was identified in humans and is expressed constitutively in the liver and, thus, is defined as a constitutive SAA (C-SAA). A similar protein that is now also called SAA4 has since been identified in the mouse; it had originally been designated SAA5.

References

References

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4. (November 1991). "Nonexpression of the human serum amyloid A three (SAA3) gene". DNA and Cell Biology.
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6. "SAA4".
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8. (May 1993). "A constitutively expressed serum amyloid A protein gene (SAA4) is closely linked to, and shares structural similarities with, an acute-phase serum amyloid A protein gene (SAA2)". Genomics.
9. (February 1994). "Mouse serum amyloid A protein (SAA5) structure and expression". The Journal of Biological Chemistry.
10. (May 1996). "Structure of the mouse Saa4 gene and its linkage to the serum amyloid A gene family". Genomics.