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

Kenji Daigo,Yuichiro Takamatsu,Takao Hamakubo

doi:10.3389/fimmu.2016.00344

Kenji Daigo, Yuichiro Takamatsu + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2016.00344

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Abstract

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.

Highlights

The innate immune system serves as the first line of defense against pathogen invasion and consists of cellular and humoral arm
The innate immune response is triggered by pattern recognition molecules (PRMs) upon the recognition of pathogen-associated molecular patterns (PAMPs), which are structural patterns conserved across a broad spectrum of microbes [1, 2]
As it is considered that neutrophil extracellular traps (NETs) are the source of extracellular histones, the protective activity of Pentraxin 3 (PTX3) against histone-mediated endothelial cell cytotoxicity implies that PTX3 participates in the regulation of NETs by attenuating the detrimental effects of NETs exerted by extracellular histones (Figure 3)

Summary

Introduction

The innate immune system serves as the first line of defense against pathogen invasion and consists of cellular and humoral arm. In addition to its activity in the innate immune system, PTX3 exerts effects in inflammation and matrix regulation [6]. As it is expected that the complex formation of PTX3 with other proteins in NETs exerts synergistic antimicrobial effects, further investigation will be needed to fully understand the activities of the NET component proteins.

Results

Conclusion