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The exact roles and abilities of the individual components of the lipopolysaccharide (LPS) receptor complex of proteins remain unclear. MD-2 is a molecule found in association with toll-like receptor 4. We produced recombinant human MD-2 to explore its LPS binding ability and role in the LPS receptor complex. MD-2 binds to highly purified rough LPS derived(More)
LPS binding protein (LBP) and CD14 play key roles in promoting innate immunity to Gram-negative bacteria by transferring LPS to the signaling receptor complex, MD-2/Toll-like receptor 4 (TLR4). LBP and soluble CD14 (sCD14) can also inhibit responses to LPS by mechanisms that depend on their concentration and environment; during acute inflammation and(More)
Vascular disease risk is inversely related to circulating levels of high-density lipoprotein (HDL) cholesterol. However, the mechanisms by which HDL provides vascular protection are unclear. The disruption of endothelial monolayer integrity is an important contributing factor in multiple vascular disorders, and vascular lesion severity is tempered by(More)
Host recognition and disposal of LPS, an important Gram-negative bacterial signal molecule, may involve intracellular processes. We have therefore analyzed the initial pathways by which LPS, a natural ligand of glycosylphosphatidylinositol (GPI)-anchored CD14 (CD14-GPI), enters CD14-expressing THP-1 cells and normal human monocytes. Exposure of the cells to(More)
Much evidence indicates that bacterial LPS (endotoxin) is removed from the bloodstream mainly by the liver, yet the hepatic uptake mechanisms remain uncertain and controversial. In plasma, LPS can be either 'free' (as aggregates, bacterial membrane fragments or loosely bound to albumin, CD14, or other proteins) or 'bound' (complexed with lipoproteins).(More)
Lipoproteins of Treponema pallidum and Borrelia burgdorferi possess potent proinflammatory properties and, thus, have been implicated as major proinflammatory agonists in syphilis and Lyme disease. Here we used purified B. burgdorferi outer surface protein A (OspA) and synthetic lipopeptides corresponding to the N-termini of OspA and the 47-kDa major(More)
Propionic and methylmalonic aciduria occur individually in inborn errors of metabolism and together in vitamin B12-deficient states. A method is described for the simultaneous and rapid extraction of these acids from urine and their quantification by a simple gas chromatographic technique. The assay is based upon the spontaneous and quantitative(More)
Lipopolysaccharides (LPS) that lack acyloxyacyl groups can antagonize responses to LPS in human cells. Although the site and mechanism of inhibition are not known, it has been proposed that these inhibitory molecules compete with LPS for a common cellular target such as a cell-surface binding receptor. In the present study, we used an in vitro model system(More)
Like other tetraacyl partial structures of lipopolysaccharide (LPS) and lipid A, LPS that has been partially deacylated by acyloxyacyl hydrolase can inhibit LPS-induced responses in human cells. To identify the site(s) of inhibition in the LPS recognition pathway, we analyzed the apparent binding affinities and interactions of 3H-labeled enzymatically(More)
CD14, a myeloid cell-surface receptor and soluble plasma protein, binds LPS and other microbial molecules and initiates the innate immune response to bacterial invasion. The blood concentration of soluble CD14 (sCD14) increases during the systemic response to infection. Although high sCD14 blood levels have correlated with increased risk of dying from(More)