[5][6][7] SAA1 is a major acute-phase protein mainly produced by hepatocytes in response to infection, tissue injury and malignancy.

[12] Two of these genes, SAA1 and SAA2, are inducible during acute-phase response, whereas SAA3 is a pseudogene in humans[13] and SAA4 is constitutively expressed in a variety of tissues and cells.

[24] SAA1 has been found to interact with outer membrane protein A (ompA) of several Gram-negative bacteria including E. coli, Salmonella typhimurium, Shigella flexneri, Vibrio cholerae and P.

As a result, SAA1 has been a clinical indicator and reliable biomarker for inflammatory diseases, chronic metabolic disorders and late-stage malignancy.

[28] Inflammatory amyloidosis results from chronic inflammation with increased production of SAA1, which is a major precursor of amyloid A fibril deposit in various tissues.

During the acute-phase response, elevated levels of SAA1 in the plasma displaces ApoA-I and becomes a major apolipoprotein of HDL.

[30] The exact biological consequence of HDL remodeling by SAA1 is still under investigation, using recently developed tools such as the Saa1 and Saa2 knockout mice.

[33] Ex vivo and in vitro studies have shown that the recombinant human SAA1 hybrid protein has strong chemotactic activity for neutrophils and macrophages.

[42] This finding, which is based on both Saa1/Saa2 knockout mice and ex vivo studies of T cells, strongly suggest a local immunomodulatory function of SAA1 as opposed to its established role as an acute-phase protein produced in the liver and present in the plasma as an apolipoprotein of HDL.

Transgenic expression of human SAA1.1 in mouse liver aggravates T cell-mediated hepatitis through elevated production of chemokines,[43] which involves the SAA1 receptor TLR2.

[49] Other studies have shown that native human SAA1 retains some of the cytokine-like activities such as the G-CSF-induction capability[50] Recent studies using the Saa1/Saa2 knockout mice showed weakened Th17 response in gut epithelial cells,[51] suggesting that SAA1 plays a role in vivo in the regulation of immunity.