title: Plasma constituents regulate LPS binding to, and release from, the monocyte cell surface.
abstract: Innate immunity to Gram-negative bacteria involves regulated mechanisms that allow sensitive but limited responses to LPS. Two important pathways that lead to host cell activation and LPS deactivation involve: (i) LPS interactions with CD14 and Toll-like receptor 4 on cells (activation); and (ii) LPS sequestration by plasma lipoproteins (deactivation). Whereas these pathways were previously thought to be independent and essentially irreversible, we found that they are connected by a third pathway: (iii) the movement of LPS from host cells to plasma lipoproteins. Our data show that, in the presence of human plasma, LPS binds transiently to monocyte surfaces and then moves from the cell surface to plasma lipoproteins. Soluble CD14 enhances LPS release from cells in the presence of lipoproteins, whereas LPS binding protein and phospholipid transfer protein do not. The transfer of cell-bound LPS to lipoproteins is accompanied by reduced cell responses to the LPS, suggesting that the movement of LPS from leukocytes into lipoproteins may attenuate host responses to LPS in vivo. Preliminary data suggest that changes that occur in the plasma after trauma or during sepsis decrease LPS binding to leukocytes while greatly increasing the rate of LPS release from cells.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9113, USA. richard.kitchens@UTSouthwestern.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Kitchens
authors.forename: P A
authors.initials: PA
authors.lastname: Thompson
authors.forename: G E
authors.initials: GE
authors.lastname: O'Keefe
authors.forename: R S
authors.initials: RS
authors.lastname: Munford
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008070:Lipopolysaccharides / Q000097:blood*; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides