Intravascular Danger Signals Guide Neutrophils to Sites of Sterile Inflammation

Inflammation Response in Living Color

Besides responding to microbial infection, our immune system also plays an important role in responding to sterile injury, for example, during trauma or organ necrosis. In a mouse model of sterile liver inflammation, McDonald et al. (p. 362 ) used dynamic in vivo imaging to visualize the innate immune response, which is dominated by neutrophils. Neutrophils were rapidly recruited to the site of inflammation through intravascular channels. Adenosine triphosphate generated from necrotic cells at the injury site and the Nlrp3 inflammasome were required for neutrophils to exit the circulation into the vascular endothelium, where they used integrins to adhere. A luminal chemokine gradient guided integrin-dependent, intravascular migration toward the site of injury. Finally, formyl peptides provided a signal to override the chemokine gradient and draw neutrophils into the site of injury.