Serum amyloid A

Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. Different isoforms of SAA are expressed constitutively (constitutive SAAs) at different levels or in response to inflammatory stimuli (acute phase SAAs). These proteins are predominantly produced by the liver.^[1] The conservation of these proteins throughout invertebrates and vertebrates suggests SAAs play a highly essential role in all animals.^[2]

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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.^[3] Three acute phase SAA isoforms have been reported in mice, called SAA1, SAA2 and SAA3. During inflammation, SAA1 and SAA2 are principally expressed and induced in the liver, while 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).^[3] Three A-SAA genes have also been identified in humans^[4], although the third gene, SAA3, is believed to represent a pseudogene that does not generate messenger RNA or protein.^[5]

Constitutive serum amyloid A proteins

A fourth SAA (SAA4) was identified in humans and is expressed constitutively in the liver thus is defined as a constitutive SAA (C-SAA).^[6] A similar protein has since been identified in the mouse that is now also called SAA4; it had originally been designated SAA5.^[7][8]

References

1. ^ Uhlar and Whitehead. Serum amyloid A, the major vertebrate acute-phase reactant Eur. J. Biochem., 1999, volume 265, pages 501-523.
2. ^ Manley et al. Rapid recycling of cholesterol: the joint biologic role of C-reactive protein and serum amyloid A. Med Hypotheses, 2006, Volume 66, pages 784-92.
3. ^ ^{a b} Zhang et al. Serum Amyloid A-Luciferase Transgenic Mice: Response to Sepsis, Acute Arthritis, and Contact Hypersensitivity and the Effects of Proteasome Inhibition. Journal of Immunology, 2005, Volume 174, pages 8125-8134.
4. ^ Betts et al., The human acute-phase serum amyloid A gene family: structure, evolution and expression in hepatoma cells, Scand J Immunol. 1991, Volume 34, pages 471-82.
5. ^ Kluve-Beckerman et al. Non-expression of the serum amyloid A three (SAA3) gene. DNA cell biol., 1991, Volume 10, pages 651-661.
6. ^ Steel et al., 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, 1993, Volume 16, Pages 447-454.
7. ^ de Beer et al. Mouse serum amyloid A protein (SAA5) structure and expression. J. Biol. Chem., 1994, Volume 269, pages 4661-4667.
8. ^ de Beer et al. Structure of the mouse Saa4 gene and its linkage to the serum amyloid A gene family. Genomics, 1996, Volume 34 pages 139-142.