We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood.
- Authors
Clark, Stephen R.; Ma, Adrienne C.; Tavener, Samantha A.; McDonald, Braedon; Goodarzi, Zahra; Kelly, Margaret M.; Patel, Kamala D.; Chakrabarti, Subhadeep; McAvoy, Erin; Sinclair, Gary D.; Keys, Elizabeth M.; Allen-Vercoe, Emma; DeVinney, Rebekah; Doig, Christopher J.; Green, Francis H. Y.; Kubes, Paul
- 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.
- Subjects
NEUTROPHILS; CARCINOGENESIS; SEPSIS; BACTERIA; BLOOD vessels; BLOOD platelets
- Publication
Nature Medicine, 2007, Vol 13, Issue 4, p463
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1565