title: Impact of sepsis-induced changes in plasma on LPS interactions with monocytes and plasma lipoproteins: roles of soluble CD14, LBP, and acute phase lipoproteins.
abstract: Sepsis-induced changes in human plasma decrease LPS association with monocytes by regulating dynamic interactions among LPS, monocytes, and plasma lipoproteins. In the physiological environment of undiluted human serum, we have found that: (i) LPS binds transiently to monocytes and is released into plasma lipoproteins; (ii) the release of LPS from monocytes is dependent upon lipoprotein acceptors and is enhanced by soluble CD14 (sCD14); and (iii) both lipoproteins and sCD14 can attenuate cytokine responses in monocytes that have already bound LPS. Whereas LPS binding protein (LBP) also inhibited LPS responses after LPS had bound to monocytes, this did not require extensive release of cell-bound LPS as was observed with sCD14. In the serum of septic patients, both free LPS and monocyte-bound LPS were usually transferred to lipoproteins at an accelerated rate. In spite of a sharp decline in HDL levels, HDL remained the dominant LPS acceptor in many severely septic patients, whereas in some cases LPS binding shifted largely to a non-HDL lipoprotein fraction that co-eluted according to size with very low-density lipoprotein (VLDL). Preliminary data suggest that these lipoproteins have a very low density, and they contain apolipoprotein E and higher than normal proportions of the total lipoprotein cholesterol, phospholipid, apolipoprotein B, and serum amyloid A. The data suggest that the VLDL fraction contains acute phase lipoproteins of significantly altered composition that can replace HDL as the dominant LPS acceptor during sepsis when HDL levels are low.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. richard.kitchens@utsouthwestern.edu
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kitchens
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Thompson
mesh_terms: D000209:Acute-Phase Proteins / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood*; D015536:Down-Regulation; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008070:Lipopolysaccharides / Q000097:blood*; D008074:Lipoproteins / Q000097:blood* / Q000276:immunology; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D018805:Sepsis / Q000097:blood* / Q000276:immunology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein