**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.

**Keywords:** SAA, inflammation, immunity

### **1. Introduction**

Serum amyloid A (SAA) was identified in early studies as the precursor of amyloid A (AA), the tissue deposit of which causes secondary amyloidosis [1–4]. SAA was also found as one of the major acute-phase proteins that are produced in large quantities by hepatocytes and released to blood circulation in response to trauma, infection, late-stage malignancy and severe stress [5, 6]. Extending from these early findings, increased levels of SAA were found both in plasma and in injured and inflammatory tissues. A large body of literature reports SAA as a biomarker in a variety of diseases ranging from acute inflammation, chronic inflammation, type-2 diabetes, malignancy and postsurgical complications [7–9]. However, the biological functions of SAA remained largely unknown for many years [10] despite efforts in it biochemical characterization, gene cloning of its isoforms, studies of the interactions between SAA and high-density lipoprotein (HDL), and delineation of its regulatory activities in inflammation and immunity. The widespread use of recombinant human SAA proteins has accelerated the characterization of the biological functions of SAA *in vitro*, but at the same time produced data that are not fully compatible with those obtained from *in vivo* studies. In the past decade, mice with genetically altered genes were prepared and their use in a number of diseases models has begun to delineate the pathophysiological functions of SAA *in vivo*. This chapter provides an overview of the studies of SAA that have been published and summarizes recent findings of the immunomodulatory functions of different SAA

proteins. For other functions of SAA, the interested reader is referred to several excellent reviews that have been published recently [9, 11–15].
