The Protective Effect against Extracellular Histones Afforded by Long-Pentraxin PTX3 as a Regulator of NETs

Kenji Daigo, Yuichiro Takamatsu, Takao Hamakubo

Pentraxin 3 (PTX3) is a soluble pattern recognition molecule that plays critical roles in innate immunity. Its fundamental functions include recognition of microbes, activation of complement cascades, and opsonization. The findings that PTX3 is one of the component proteins in neutrophil extracellular traps (NETs) and binds with other NET proteins imply the importance of PTX3 in the NET-mediated trapping and killing of bacteria. As NETs play certain critically important host-protective roles, aberrant NET production results in tissue damage. Extracellular histones, the main source of which is considered to be NETs, are mediators of septic death due to their cytotoxicity toward endothelial cells. PTX3 protects against extracellular histones-mediated cytotoxicity through coaggregation. In addition to the anti-bacterial roles performed in coordination with other NET proteins, PTX3 appears to mitigate the detrimental effect of over-activated NETs. A better understanding of the role of the PTX3 complexes in NETs would be expected to lead to new strategies for maintaining a healthy balance between the helpful bactericidal and undesirable detrimental activities of NETs.