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Review
. 2023 Dec 7:14:1324021.
doi: 10.3389/fimmu.2023.1324021. eCollection 2023.

Crosstalk between neutrophil extracellular traps and immune regulation: insights into pathobiology and therapeutic implications of transfusion-related acute lung injury

Yi Liu #  1 , Rong Wang #  2 , Congkuan Song #  1 , Song Ding  1 , Yifan Zuo  1 , Ke Yi  1 , Ning Li  1 , Bo Wang  1 , Qing Geng  1
Affiliations
Review

Crosstalk between neutrophil extracellular traps and immune regulation: insights into pathobiology and therapeutic implications of transfusion-related acute lung injury

Yi Liu et al. Front Immunol. .

Abstract

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated death, occurring during or within 6 hours after transfusion. Reports indicate that TRALI can be categorized as having or lacking acute respiratory distress syndrome (ARDS) risk factors. There are two types of TRALI in terms of its pathogenesis: antibody-mediated and non-antibody-mediated. The key initiation steps involve the priming and activation of neutrophils, with neutrophil extracellular traps (NETs) being established as effector molecules formed by activated neutrophils in response to various stimuli. These NETs contribute to the production and release of reactive oxygen species (ROS) and participate in the destruction of pulmonary vascular endothelial cells. The significant role of NETs in TRALI is well recognized, offering a potential pathway for TRALI treatment. Moreover, platelets, macrophages, endothelial cells, and complements have been identified as promoters of NET formation. Concurrently, studies have demonstrated that the storage of platelets and concentrated red blood cells (RBC) can induce TRALI through bioactive lipids. In this article, recent clinical and pre-clinical studies on the pathophysiology and pathogenesis of TRALI are reviewed to further illuminate the mechanism through which NETs induce TRALI. This review aims to propose new therapeutic strategies for TRALI, with the hope of effectively improving its poor prognosis.

Keywords: immune regulation; neutrophil; neutrophil extracellular traps; therapy; transfusion-related acute lung injury.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview of mechanisms of TRALI development.
Figure 2
Figure 2
NETs formation and its intrinsic immune regulation of NETs formation. (A) NETs formation and the inflammatory pathway intrinsic to neutrophils. NADPH or mitochondrial ROS stimulates the sequential activation of neutrophil MPO and NE, followed by NE entering intranucleus to cleave histones, combined with histone citrullination of PAD 4 promoting chromatin decondensation. Subsequently, under the pore-forming action of GSDMD, the DNA network within the nucleus binds a variety of proteins to release into the extracellular cell. This process is usually affected by the cGAS, NLRP 3 signaling pathway. (B) The glucose metabolism in neutrophils. In the resting state, glycolysis is the primary way neutrophils acquire energy, where activated glycolysis is enhanced and a larger fraction of glucose enters the pentose phosphate pathway to support the ROS required to produce respiratory burst and NETs.
Figure 3
Figure 3
Extrinsic immunomodulation of neutrophils in NETs.
Figure 4
Figure 4
Therapeutic implications.
See this image and copyright information in PMC

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Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the National Natural Science Foundation of China (No. 8210082163, 81800343), the Fundamental Research Funds for the Central Universities (No. 2042021kf0081).
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