A Neutrophil-like Cell Model as Substitute for Human Neutrophils in NETs and Thrombosis Research

TL;DR

This paper explores using PLB-985 cells as a substitute for human neutrophils to study NETs and their role in blood clotting.

Contribution

The study introduces PLB-985 cells as a viable alternative to human neutrophils for NET and thrombosis research.

Findings

PLB-985-derived NETs show similar fibrin fiber thickness and morphology to human neutrophil-derived NETs.

PLB-985-derived NETs contain spherical particles resembling microvesicles, potentially contributing to procoagulant effects.

Abstract

Neutrophil extracellular traps (NETs) critically influence thrombosis by promoting platelet aggregation, fibrin formation, and thrombus stabilisation. However, primary human neutrophils present experimental limitations, including short lifespan ex vivo and ethical concerns. In this article, we discuss the available data on PLB-985 cells, a neutrophil-like model with potential to replace human neutrophils in research. Additionally, we present novel structural comparisons showing that both PLB-985- and human neutrophil-derived NETs significantly increased fibrin fibre thickness compared to thrombin-only controls, with similar fibre morphology across conditions. Notably, we also see spherical particles resembling microvesicles within PLB-985-derived NETs, suggesting potential additional procoagulant effects via microvesicle-associated tissue factor level in these cells. New and existing data presented in this article suggest that differentiated PLB-985 cells are able to effectively replicate key structural and functional aspects of human neutrophil NETs. These observations support the use of PLB-985 cells as an ethical, reproducible, and practical alternative for in vitro studies of NETs. Further characterisation is required to determine differences between human neutrophils and neutrophil-like models in macrovesicle formation and implication in NET-related thrombosis research.

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