Pentraxin 3, also known as TSG-14, was initially identified as a TNF-alpha or IL-1 beta inducible gene (1‑3). It belongs to the pentraxin family, which was named originally for the homo-pentameric structure formed by its members (4). The pentraxin family is divided into two subfamilies: the “short” and the “long” pentraxins with approximate molecular weights of 25 kDa and 50 kDa, respectively. TSG-14 is a member of the long pentraxin subfamily, which also includes the Xenopus laevis XL-PXN1, the guinea pig apexin/p50, the rat neuronal pentraxin I (NPI) and NPR, the human neuronal pentraxin II (NPTX2) and the human neuronal activity-related pentraxin (5).
Mature secreted PTX3 contains a pentaxin-like domain at its carboxy-terminus that shares 23‑28% amino acid (aa) sequence similarity to C-reactive protein (CRP) and serum amyloid P component (SAP), which belong to the short pentraxin subfamily. However, the N-terminal sequence of TSG-14 does not share aa sequence homology with any of the “short” pentaxins (3). Unlike CRP and SAP, which forms pentamers only, TSG-14 forms both pentameric and higher ordered oligomers (5). Similar to CRP and SAP, TSG-14 binds to the complement cascade component C1q (6). However, TSG-14 does not bind to phosphoethanolamine, phosphocholine, or high pyruvate agarose, which are known ligands for CRP and SAP. While CRP and SAP are primarily produced in the liver, TSG-14 expression is strongly up‑regulated by TNF-alpha, IL-1 beta, and bacterial LPS in peripheral fibroblasts, endothelial cells, and macrophages (7). At the amino acid level, human and mouse TSG-14 share 88% aa sequence homology (8). TSG-14 concentration is elevated in the joint fluid of patients with rheumatoid arthritis (RA), indicating that TSG-14 may be a potential mediator of immune response (9). TSG-14 may also function in the regulation of the uptake and clearance of apoptotic cells by dendritic cells (10). An in vivo study showed that TSG-14 transgenic mice are more resistant to sepsis and endotoxemia compared to wild-type during inflammatory injury (11). Increased expression of TSG-14 may enhance the immune response to protect the host from infection.
