Serum Amyloid A and Immunomodulation

Abstract

Serum amyloid A1 (SAA1), a major isoform of acute-phase SAA, is a well-known precursor of amyloid A (AA) that contributes to secondary amyloidosis with its tissue deposition. Acute-phase SAA is also a biomarker of inflammation. Recent studies have focused on the roles for acute-phase SAA in the regulation of immunity and inflammation. In vitro characterization of recombinant human SAA identified its chemotactic and cytokine-like properties, whereas the use of SAA isoform-specific transgenic and knockout mice has led to the discovery of new functions of SAA proteins in host defense and tissue homeostasis. Characterization of SAA-derived peptides has shown that fragments of SAA, generated through proteolysis, are bioactive and may contribute to a growing list of functions related to inflammation. This chapter summarizes recent progress in the studies of acute-phase SAA and its fragments in inflammation and immunomodulation.

Serum amyloid A3 confers protection against acute lung injury inPseudomonas aeruginosa-infected mice

“…There is an extensive literature documenting elevated SAA expression and its correlation with clinical diseases ranging from rheumatoid arthritis and atherosclerosis to Type 2 diabetes and solid tumors (29). However, the physiological functions of SAA only began to be delineated when recombinant SAA was found to have chemotactic and proinflammatory properties (11). In vitro studies suggest that increased SAA expression, which accompanies all inflammatory diseases, may exacerbate inflammation through its ability to induce the expression of inflammatory cytokines and tissue-degrading proteases (6).…”

N-terminal peptide fragment constitutes core of amyloid deposition of serum amyloid A: An imaging mass spectrometry study

“…SAA1 is cleaved by MMP9 and its C-terminal fragments cooperate with CXCL8 to activate and migrate neutrophils [32]. Cathepsins, which are endosomal and lysosomal proteases, have also been shown to cleave SAA [33]. Cathepsin B cleaves SAA at residues 76-77 to produce the most common form of AA found in amyloidosis [34,35].…”

Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation

“…SAA is induced by various proinflammatory cytokines, such as interleukin-1b (IL-1b), IL-6, and tumor necrosis factor a (TNF-a) (19-21). Biologically, SAA appears to have a broad range of activities mediated by various receptors, suggesting not only as a biomarker but also to be an integral center of inflammatory signals (22,23).…”