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

Nature Medicine 13: 463-469 (2007)

Speaker: 李明翰                          Time: 14:10~15:00, Jun. 6, 2007

Commentator: 劉清泉 醫師                Place: Room 601

Abstract:

Neutrophils are important in defense against bacterial infection. Neutrophils are known to primarily kill bacteria by phagocytosis. Recently, an alternative mechanism whereby activation of neutrophils causes formation of a web-like DNA structure known as neutrophil extracellular traps (NETs) to ensnare and kill bacteria. Bacteremia or endotoxemia can inappropriately activate neutrophils migrating to the capillaries of the lungs and the sinusoids of the liver. Additionally, it is known that many platelets can also localize to both the lung and liver in sepsis. These previous findings imply that platelets and neutrophils may be involved in fighting against bacterial infection. Previous reports indicated that TLR4 is expressed on both human and mouse platelets. In this study, the authors demonstrated that following LPS stimulation, platelets could interact with neutrophils, leading to the rapid formation of NETs. These NETs mediated bacterial trapping in the liver sinusoids and pulmonary capillaries where they have the greatest capacity for capture. They also suggested that this event would cause damage to the endothelium and surrounding tissues. This provides evidence that TLR4-stimulated platelets act as a threshold switch for a novel bacterial trapping mechanism by neutrophils in severe sepsis.

References:

1.      Brinkmann, V. et al. 2004. Neutrophil extracellular traps kill bacteria. Science 303: 1532-1535.

2.      Andonegui, G. et al. 2005. Platelets express functional Toll-like receptor-4. Blood 106: 2417-2423.