title: Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood.
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.
authors: Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
authors: Stephen R
authors: SR
authors: Clark
authors: Adrienne C
authors: AC
authors: Ma
authors: Samantha A
authors: SA
authors: Tavener
authors: Braedon
authors: B
authors: McDonald
authors: Zahra
authors: Z
authors: Goodarzi
authors: Margaret M
authors: MM
authors: Kelly
authors: Kamala D
authors: KD
authors: Patel
authors: Subhadeep
authors: S
authors: Chakrabarti
authors: Erin
authors: E
authors: McAvoy
authors: Gary D
authors: GD
authors: Sinclair
authors: Elizabeth M
authors: EM
authors: Keys
authors: Emma
authors: E
authors: Allen-Vercoe
authors: Rebekah
authors: R
authors: Devinney
authors: Christopher J
authors: CJ
authors: Doig
authors: Francis H Y
authors: FH
authors: Green
authors: Paul
authors: P
authors: Kubes
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001419:Bacteria / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D018805:Sepsis / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D000410:Alanine Transaminase