Host-protective effect of circulating pentraxin 3 (PTX3) and complex formation with neutrophil extracellular traps

Abstract

Pentraxin 3 (PTX3) is a soluble pattern recognition receptor which is classified as a long-pentraxin in the pentraxin family. It is known to play an important role in innate immunity, inflammatory regulation, and female fertility. PTX3 is synthesized by specific cells, primarily in response to inflammatory signals. Among these various cells, neutrophils have a unique PTX3 production system. Neutrophils store PTX3 in neutrophil-specific granules and then the stored PTX3 is released and localizes in neutrophil extracellular traps (NETs). Although certain NET components have been identified, such as histones and anti-microbial proteins, the detailed mechanisms by which NETs localize, as well as capture and kill microbes, have not been fully elucidated. PTX3 is a candidate diagnostic marker of infection and vascular damage. In severe infectious diseases such as sepsis, the circulating PTX3 concentration increases greatly (up to 100 ng/mL, i.e., up to 100-fold of the normal level). Even though it is clearly implied that PTX3 plays a protective role in sepsis and certain other disorders, the detailed mechanisms by which it does so remain unclear. A proteomic study of PTX3 ligands in septic patients revealed that PTX3 forms a complex with certain NET component proteins. This suggests a role for PTX3 in which it facilitates the efficiency of anti-microbial protein pathogen clearance by interacting with both pathogens and anti-microbial proteins. We discuss the possible relationships between PTX3 and NET component proteins in the host protection afforded by the innate immune response. The PTX3 complex has the potential to be a highly useful diagnostic marker of sepsis and other inflammatory diseases.