Pentraxin 2 (PTX2), also known as Serum Amyloid P Component (SAP), is a secreted serum glycoprotein that is a universal non-fibrillar component of amyloid deposits. These extracellular deposits of insoluble protein fibrils are the result of protein misfolding and can lead to tissue damage and disease (1, 2). PTX2 belongs to the pentaxin superfamily, whose members have the characteristic pentagonal discoid arrangement of five non-covalently bound subunits. Pentaxins bind to a variety of molecules in a calcium-dependent lectin-like manner through a pattern-recognition-binding site (1, 4, 5). Two subfamilies of pentaxins, the classical or short pentaxin subfamily that includes the serum C-reactive protein (CRP) and PTX2, and the fusion or long pentaxin subfamily whose members contain pentaxin-related carboxyl‑terminal halves, are known (1).
PTX2 and CRP share approximately 50% amino acid sequence identity (2, 5). They are produced and secreted by liver hepatocytes and circulates in plasma. Rat and mouse PTX2 are major acute-phase proteins whose plasma concentrations increase dramatically during an acute phase response (2). In human where CRP is the major acute-phase protein, the plasma concentration of human PTX2 remains relatively constant in response to tissue-damage (2, 5). The gene for PTX2 has been localized to rat chromosome 13 of 23 where it is closely linked to the gene for CRP.
PTX2 associates ubiquitously with all amyloid deposits that are implicated in a diverse range of diseases including Alzheimer’s and prion diseases, type 2 diabetes and various systemic amyloidoses (3, 6, 7). As a non-fibrillar component, PTX2 regulates the solubility of amyloid fibrils and protects them from degradation by proteolytic enzymes and phagocytic cells. In addition to its role in the pathogenesis of amyloidoses, PTX2 also has an important physiological function in innate immunity (8). It is an opsonin that interacts with all three types of human Fc gamma receptors that mediate phagocytosis by polymorphonuclear leukocytes. It has been proposed that PTX2 may function as an opsonin for a variety of ligands including autoantigens, apoptotic cells, chromatin, DNA, and micro-organisms.
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