Pentraxin-related protein PTX3 also known as TNF-inducible gene 14 protein (TSG-14) is a protein that in humans is encoded by the PTX3 gene.
Gene location Chromosome 3 (human)
Pentraxin 3 (ptx3) is a member of the pentraxin superfamily.
PTX3 is produced and released by several cell types: mononuclear phagocytes, dendritic cells (DCs), fibroblasts and endothelial cells in response to primary inflammatory signals such as toll-like receptor (TLR) engagement, TNFα, IL-1β.
PTX3 binds with high affinity to the complement component C1q, the TNFα induced protein 6 and selected microorganisms, including Aspergillus fumigatus and Pseudomonas aeruginosa.
PTX3 activates the classical pathway of complement activation and facilitates recognition by macrophages and dendritic cells.
PTX3 behaves as an acute phase response protein, as the blood levels of PTX3, low in normal conditions (< 2 ng/mL in humans), increase rapidly, peaking at 6–8 h after induction and dramatically (200–800 ng/mL) during endotoxic shock, sepsis and other inflammatory and infectious conditions, correlating with the severity of the disease.
PTX3 levels in cerebrospinal fluid help distinguishing between bacterial and aseptic meningoencephalitis.
Under these conditions, PTX3 is a rapid marker for primary local activation of innate immunity and inflammation.
Similar to other members of the pentraxin family PTX3 binds apoptotic cells, thereby inhibiting their recognition by dendritic cells.
Binding occurs late in the apoptotic process and enhances cytokine production by DCs.
Preincubation of apoptotic cells with PTX3 enhances C1q binding and C3 deposition on the cell surface, suggesting a role for PTX3 in the complement-mediated clearance of apoptotic cells.
Moreover, in the presence of dying cells, PTX3 restricts the cross presentation of antigens derived from dying cells.
These results suggest that PTX3 has a dual role: protection against pathogens and control of autoimmunity.
PTX3 levels reflect the severity of inflammatory vascular diseases ranging from atherosclerosis to vasculitis.
PTX3 levels increase earlier than C-reactive protein levels in inflammatory processes.
PTX3 is stored in neutrophil granules.
PTX3 serves as an immediate early gene in tissues, with its transcription induced by TLR agonists and inflammatory cytokines.
C-reactive protein production in the liver occurs downstream of the cytokine cascade, which results in a later appearance.
PTX3 and SAP genetic polymorphisms have been associated with susceptibility to fungal and bacterial infections and to lung granuloma formation in sarcoidosis through regulation of complement.