Neutrophils (red) adhere to an adhesion molecule called SHAP (green) in liver blood capillaries (arrows).

Activated neutrophils that infiltrate the liver during severe sepsis lodge themselves in the liver's tiniest blood vessels and cause organ damage. On page 915, McDonald et al. examine how neutrophils burrow into the liver and suggest a way to pry them out.

Neutrophil recruitment in response to sepsis-triggering bacterial toxins such as LPS unfolds in several stages. In most places in the body, adhesion molecules called selectins initially snare neutrophils and help them tether to and roll along blood vessel walls. The cells subsequently adhere more firmly through integrins. But because neutrophils do not seem to need these molecules to stick to the blood capillaries in the liver, researchers suspected that the narrowness of these vessels instead physically traps the neutrophils.

McDonald et al. now provide evidence against this entrapment model by showing that neutrophils are snagged by a different adhesion molecule, hyaluronan (HA), which they found at high levels in liver vessels. When mice were injected with LPS, neutrophil adhesion levels increased 14 fold, although HA levels did not change. The increased adhesiveness may be due to an HA-associated protein called SHAP, which increases HA's affinity for its neutrophil cell surface ligand, CD44. SHAP levels on the liver's capillary walls were increased by LPS treatments.

Disrupting the interaction between CD44 and HA might potentially reverse sepsis; injecting LPS-treated mice with an anti-CD44 antibody rapidly detached neutrophils from the liver capillary walls and decreased liver damage.