Cited by 2,309Neutrophil, Myeloperoxidase and Oxidative MechanismsInflammation biomarkers and pathwaysSepsis Diagnosis and Treatment

Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood

Clark, Stephen R, Ma, Adrienne C, Tavener, Samantha A, McDonald, Braedon, Goodarzi, Zahra, Kelly, Margaret M, Patel, Kamala D, Chakrabarti, Subhadeep +8 more·2007·Nature Medicine

Abstract

It has been known for many years that neutrophils and platelets participate in the pathogenesis of severe sepsis, but the inter-relationship between these players is completely unknown. We report several cellular events that led to enhanced trapping of bacteria in blood vessels: platelet TLR4 detected TLR4 ligands in blood and induced platelet binding to adherent neutrophils. This led to robust neutrophil activation and formation of neutrophil extracellular traps (NETs). Plasma from severely septic humans also induced TLR4-dependent platelet-neutrophil interactions, leading to the production of NETs. The NETs retained their integrity under flow conditions and ensnared bacteria within the vasculature. The entire event occurred primarily in the liver sinusoids and pulmonary capillaries, where NETs have the greatest capacity for bacterial trapping. We propose that platelet TLR4 is a threshold switch for this new bacterial trapping mechanism in severe sepsis.

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Crossref · 10.1038/nm1565

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Authors
Clark, S. R., Ma, A. C., Tavener, S. A., McDonald, B., Goodarzi, Z., Kelly, M. M., Patel, K. D., Chakrabarti, S., McAvoy, E., Sinclair, G. D., Keys, E. M., Allen-Vercoe, E., DeVinney, R., Doig, C. J., Green, F. H. Y., & Kubes, P.
Affiliations
University of Calgary (CA)
Corresponding author
Kubes, Paul
Venue
Nature Medicine
Published
2007-03-25
Volume
13
Issue
4
Pages
463-469
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W1986282241
Cited by
2,309
References
38
Citations by year
2026: 100 · 2025: 136 · 2024: 104 · 2023: 152 · 2022: 200 · 2021: 189 · 2020: 167 · 2019: 175 · 2018: 137 · 2017: 146 · 2016: 124 · 2015: 131 · 2014: 119 · 2013: 112 · 2012: 105
FWCI
17.96
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
  • Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
Keywords
neutrophil extracellular traps, sepsis, neutrophil-platelet interaction, bacterial trapping, neutrophil activation, liver sinusoids, pulmonary capillaries, sepsis pathogenesis, threshold switches
MeSH terms
Alanine Transaminase, Animals, Bacteria, Blood Platelets, Epithelium, Humans, Lipopolysaccharides, Liver, Neutrophils, Sepsis, Toll-Like Receptor 4, Mice

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