Innate immune recognition of lipopolysaccharide by endothelial cells

Objective. The endothelium is an active component of the innate immune response to bacterial invasion. Endothelial cells comprise mechanisms to recognize structural patterns expressed by pathogens and subsequently initiate the transcription of inflammatory genes. The purpose of this article is to summarize the molecular processes that underlie the endothelial innate immune response to microbial components, with a particular focus on responses to Gram-negative bacterial lipopolysaccharide. Data Sources: Personal observations and review of the literature as revealed by the National Library of Medicine. Data Summary and Conclusion: Endothelial cells recognize the presence of microbial components such as lipopolysaccharide via a receptor complex that contains at least three important cell surface components: CD14, Toll-like receptor-4, and MD-2. CD14 and MD-2 exist as soluble receptor components and are thought to bind to both lipopolysaccharide and Toll-like receptor-4, whereas Toll-like receptor-4 itself is the transmembrane signal transducer. Single-point mutations in MD-2 or the cytoplasmic portion of Toll-like receptor-4 abrogate the response to lipopolysaccharide. The composition of this receptor and the recruitment and activation of various cytoplasmic proteins afford at least five levels of ligand specificity and suggest that there are at least as many potential therapeutic targets for Toll-like receptor-mediated inflammatory states, including sepsis.