Intravascular bacteria are optimally captured via platelet-induced NET release and resident vascular macrophages. (A) Platelet activation is essential for in vivo NETosis. Isolated neutrophils become activated at very low levels of LPS; however, platelet activation occurs at significantly higher LPS concentrations, suggesting that platelet activation acts as an inflammatory barometer to maximally stimulate neutrophils during periods of severe infection. (B) In vivo, Kupffer cells are considered the major cell involved in intravascular bacterial capture. However, under basal conditions, when NETs are not yet present, Kupffer cells only account for a third of the microbial trapping. Similarly, under LPS-stimulated conditions, depletion of PMNs resulting in NET deficiency yields levels of capture similar to Kupffer cells alone. Hence, optimal bacterial capture occurs when Kupffer cells, PMNs, and NETs are present. (C) In vivo, during endotoxemia, platelet depletion diminishes neutrophil activation and NET release, thereby impairing optimal bacterial capture. EC50, 50% effective concentration.
