Pentraxins

Abstract

Synonyms C-reactive protein (CRP) or PTX1; Pattern recognition molecule; PTX3; Serum amyloid protein (SAP) or PTX2. Definition Pentraxins are a superfamily of evolutionary conserved proteins with multifunctional properties in innate immunity, including complement activation and opsonization (Fig. 1). Based on the primary structure, pentraxins are divided into two subfamilies: short and long pentraxins. Prototypes of the short pentraxin family are C-reactive protein (CRP, named for its ability to bind the C polysaccharide of Streptococcus pneumoniae) and serum amyloid P (SAP) component, both identified at the beginning of the last century as acute-phase protein in men and mouse, respectively. CRP and SAP are also known as PTX1 and PTX2, respectively. More recently, the long pentraxin PTX3 has been identified as early-induced gene by primary proinflammatory signals (Bottazzi et al. 2010; Garlanda et al. 2005). PTX3 is characterized by a C-terminal pentraxin-like domain homologous to CRP and a long N-terminal domain unrelated to other known proteins. PTX3 and CRP share fundamental functions as fluid-phase pattern recognition molecules (PRMs); however, they differ in structural features and pattern of expression. Unlike CRP, the sequence and regulation of PTX3 are conserved from mouse to man, this favoring a genetic approach to understand the in vivo roles of the protein. Gene-modified animals have been essential to reveal the multifunctional properties of PTX3 at the crossroad between innate immunity, inflammation, matrix deposition, and female fertility. Biosynthesis and Release CRP and SAP genes are located on chromosome 1 in close physical and genetic linkage. CRP and SAP are expressed by hepatocytes and constitute the main acute-phase proteins in human and mouse, respectively (Bottazzi et al. 2010). In human, the baseline level of circulating CRP is low (5 mg/ml) and increases rapidly and dramatically (1000-fold) in several pathological inflammatory conditions, with a sharp rise within 6 h of induction and a maximum at approximately 48 h. In contrast, SAP is the major acute-phase protein in the mouse, and its concentration level in plasma of healthy human (30–50 mg/ml) is not modified in inflammatory conditions (Mantovani et al. 2013). The PTX3 gene is remarkably conserved across evolutionary distant species in terms of sequence, structural organization, and regulation. For example, both human and murine PTX3 genes localize on chromosome 3 and comprise three exons coding for leader peptide and N-and C-terminal domains of the