title: Cellular activation mechanisms in septic shock.
abstract: Septic shock is an increasingly important clinical condition, characterized by systemic hypotension, ischemia, and ultimately organ failure. In Gram negative infection, the bacterial cell wall component, lipopolysaccharide (endotoxin, LPS), has been strongly linked to the pathophysiological responses that result in septic shock. LPS is bound in plasma to a protein called LPS-binding protein (LBP), which facilitates the binding of LPS to a cell surface receptor, CD14. Binding to CD14 stimulates cell signaling mechanisms that result in the production of inflammatory cytokines. However, the events which follow LPS binding to CD14 and which lead to the production of cytokines remain unclear. It has recently become evident that a number of phosphorylation cascades including MAP kinase pathways and NF-kappaB activation pathway are initiated by exposure of cells to LPS. These cascades act at both the transcriptional and translational levels to regulate cytokine production. This review will focus on the signaling pathways that are initiated by LPS and the cellular effects of the signaling pathways.
authors.affiliation: Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla,, CA 92037, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Downey
authors.forename: J
authors.initials: J
authors.lastname: Han
mesh_terms: D016905:Gram-Negative Bacterial Infections / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012772:Shock, Septic / Q000201:enzymology / Q000378:metabolism* / Q000382:microbiology; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D019061:src-Family Kinases; D011493:Protein Kinase C