McDonald Braedon, Kubes Paul
Calvin, Phoebe, and Joan Snyder Institute for Infection, Immunity, and Inflammation, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
Toxicol Pathol. 2012;40(2):157-65. doi: 10.1177/0192623311427570. Epub 2011 Nov 21.
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.
肝脏是许多感染性和非感染性病因引起的炎症性疾病的靶器官。作为先天性免疫系统的关键效应器,中性粒细胞对抵御微生物感染至关重要,但在疾病状态下,它们往往是对宿主组织造成严重附带损害的根源。在这篇基于作者在2011年毒理病理学会年度研讨会上发言的文章中,他们回顾了中性粒细胞在败血症/内毒素血症以及无菌性炎症反应中被募集到肝脏的分子机制,并讨论了中性粒细胞在应对这些不同损伤时在分子动态过程中的差异。此外,作者还讨论了严重败血症期间中性粒细胞在肝脏微血管中的功能作用,包括它们对宿主防御和器官损伤的作用。鉴于不适当的嗜中性粒细胞炎症促成了许多肝脏疾病的发病机制,深入了解调节中性粒细胞向肝脏募集的分子机制及其在其中的功能,可能会揭示治疗炎症性肝脏疾病的新治疗途径。