Neutrophils and Intravascular Immunity in the Liver during Infection and Sterile Inflammation

The liver is a target of many inflammatory pathologies of both infectious and noninfectious etiology. As key effectors of the innate immune system, neutrophils are critical for defense against microbial infections but are often the source of profound collateral damage to host tissues during disease states. In this article based on the authors' presentation at the 2011 Society of Toxicologic Pathology Annual Symposium, they review the molecular mechanisms of neutrophil recruitment to the liver in response to sepsis/endotoxemia, as well as sterile inflammation, and discuss variations in the molecular choreography of neutrophil trafficking in response to these different insults. Furthermore, the authors discuss the functional contributions of neutrophils within the liver microvasculature during severe sepsis, including their contributions to both host defense and organ damage. Given that inappropriate neutrophilic inflammation contributes to the pathogenesis of many liver diseases, a thorough understanding of the molecular mechanisms that regulate the recruitment of neutrophils to the liver, and their functions therein, may reveal new avenues for therapeutic interventions to treat inflammatory liver pathologies.