Neutrophil Extracellular Traps (NETs), Immunothrombosis and the Microvascular Siege in Sepsis‐ARDS
9 affiliations
- 1Internal Medicine, Diabetes, Endocrinology and Metabolism Mansoura University Mansoura Egypt
- 2Department of Traumatology, Orthopedics, Neurosurgery and Ophthalmology Samarkand State Medical University Samarkand Uzbekistan
- 3Department‐College of Pharmacy, Department of Pharmacy Practice University‐Dubai Medical University Dubai United Arab Emirates
- 4Department of Microbiology and Clinical Parasitology King Khalid University Abhā Saudi Arabia
- 5University Institute of Pharma Sciences, Chandigarh University Mohali India
- 6Department of General Medicine Sharda University Greater Noida India
- 7Department of Pharmacy Al‐Mustafa University Baghdad Iraq
- 8College of Applied Sciences University of Technology Baghdad Iraq
- 9Hourani Center for Applied Scientific Research Al‐Ahliyya Amman University Amman Jordan
Abstract
Sepsis‐associated acute respiratory distress syndrome (ARDS) remains associated with substantial mortality despite decades of research, and the reasons why many disease‐modifying treatments have failed remain incompletely understood. This narrative review synthesizes emerging evidence implicating neutrophil extracellular traps (NETs) in the interaction between innate immunity, immunothrombosis, and microvascular failure in sepsis‐ARDS. NETs, extruded lattices of DNA, histones, and granular enzymes, serve as antimicrobial scaffolds but may contribute to tissue injury when excessive or persistent. Within the pulmonary microcirculation, experimental studies indicate that NETs can concentrate tissue factor and proteases, activate platelets, suppress fibrinolysis, and injure endothelium through histone cytotoxicity, supporting a self‐amplifying thrombo‐inflammatory loop. These processes may contribute to microvascular obstruction and barrier dysfunction, although their relative importance varies across experimental models and patient populations. We critically evaluate emerging NET‐directed interventions, including peptidylarginine deiminase 4 (PAD4) inhibition to prevent NET formation, recombinant deoxyribonuclease (DNase) to dismantle existing scaffolds, targeted neutralization of NET components (citrullinated histones), and selective anticoagulation targeting factor XII/XI. Challenges of timing, infection risk, and patient heterogeneity support further evaluation of biomarker‐guided “NET‐otyping” using plasma myeloperoxidase‐DNA, citrullinated histone H3, and experimental molecular imaging. Building on existing work in microvascular protection, we examine whether more effective and selective NET targeting could improve treatment of sepsis‐ARDS. Clinical benefit remains to be established.
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BibTeX
@article{elsehrawy2026neutrophil,
title = {{Neutrophil Extracellular Traps (NETs), Immunothrombosis and the Microvascular Siege in Sepsis‐ARDS}},
author = {Amr Ali Mohamed Abdelgawwad El‐Sehrawy and Djaloliddin Mansurov and MIRZA R. Baig and Ihab M. Abdelrahim and Neeraj Bainsal and Pankaj Bansal and Sarmad S. Abdullah and Zeina T. Khaleel and Majid S. Jabir and Aseel Smerat},
journal = {Pulmonary Circulation},
year = {2026},
month = oct,
doi = {10.1002/pul2.70438},
url = {https://doi.org/10.1002/pul2.70438},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Neutrophil Extracellular Traps (NETs), Immunothrombosis and the Microvascular Siege in Sepsis‐ARDS
AU - Amr Ali Mohamed Abdelgawwad El‐Sehrawy
AU - Djaloliddin Mansurov
AU - MIRZA R. Baig
AU - Ihab M. Abdelrahim
AU - Neeraj Bainsal
AU - Pankaj Bansal
AU - Sarmad S. Abdullah
AU - Zeina T. Khaleel
AU - Majid S. Jabir
AU - Aseel Smerat
PY - 2026
DA - 2026/10/26
JO - Pulmonary Circulation
DO - 10.1002/pul2.70438
UR - https://doi.org/10.1002/pul2.70438
AB - Sepsis‐associated acute respiratory distress syndrome (ARDS) remains associated with substantial mortality despite decades of research, and the reasons why many disease‐modifying treatments have failed remain incompletely understood. This narrative review synthesizes emerging evidence implicating neutrophil extracellular traps (NETs) in the interaction between innate immunity, immunothrombosis, and microvascular failure in sepsis‐ARDS. NETs, extruded lattices of DNA, histones, and granular enzymes, serve as antimicrobial scaffolds but may contribute to tissue injury when excessive or persistent. Within the pulmonary microcirculation, experimental studies indicate that NETs can concentrate tissue factor and proteases, activate platelets, suppress fibrinolysis, and injure endothelium through histone cytotoxicity, supporting a self‐amplifying thrombo‐inflammatory loop. These processes may contribute to microvascular obstruction and barrier dysfunction, although their relative importance varies across experimental models and patient populations. We critically evaluate emerging NET‐directed interventions, including peptidylarginine deiminase 4 (PAD4) inhibition to prevent NET formation, recombinant deoxyribonuclease (DNase) to dismantle existing scaffolds, targeted neutralization of NET components (citrullinated histones), and selective anticoagulation targeting factor XII/XI. Challenges of timing, infection risk, and patient heterogeneity support further evaluation of biomarker‐guided “NET‐otyping” using plasma myeloperoxidase‐DNA, citrullinated histone H3, and experimental molecular imaging. Building on existing work in microvascular protection, we examine whether more effective and selective NET targeting could improve treatment of sepsis‐ARDS. Clinical benefit remains to be established.
SN - 2045-8932
SN - 2045-8940
ER -