Title:Structure and Expression of Different Serum Amyloid A (SAA) Variants and their Concentration-Dependent Functions During Host Insults
Volume: 23
Issue: 17
Author(s): Mieke De Buck, Mieke Gouwy, Ji Ming Wang, Jacques Van Snick, Ghislain Opdenakker, Sofie Struyf and Jo Van Damme
Affiliation:
Keywords:
SAA variants, FPR2, TLR2, leukocytes, chemotaxis, cytokines, inflammatory diseases, amyloidosis.
Abstract: Serum amyloid A (SAA) is, like C-reactive protein (CRP), an acute phase protein
and can be used as a diagnostic, prognostic or therapy follow-up marker for many diseases. Increases in serum
levels of SAA are triggered by physical insults to the host, including infection, trauma, inflammatory reactions
and cancer. The order of magnitude of increase in SAA levels varies considerably, from a 10- to 100-
fold during limited inflammatory events to a 1000-fold increase during severe bacterial infections and acute
exacerbations of chronic inflammatory diseases. This broad response range is reflected by SAA gene duplications
resulting in a cluster encoding several SAA variants and by multiple biological functions of SAA. SAA
variants are single-domain proteins with simple structures and few post-translational modifications. SAA1
and SAA2 are inducible by inflammatory cytokines, whereas SAA4 is constitutively produced. We review
here the regulated expression of SAA in normal and transformed cells and compare its serum levels in various
disease states. At low concentrations (10-100 ng/ml), early in an inflammatory response, SAA induces
chemokines or matrix degrading enzymes via Toll-like receptors and functions as an activator and chemoattractant
through a G protein-coupled receptor. When an infectious or inflammatory stimulus persists, the liver
continues to produce more SAA (≥ 1000 ng/ml) to become an antimicrobial agent by functioning as a direct
opsonin of bacteria or by interference with virus infection of host cells. Thus, SAA regulates innate and adaptive
immunity and this information may help to design better drugs to treat specific diseases.
