title: The C-terminal Domain Supports a Novel Function for CETPI as a New Plasma Lipopolysaccharide-Binding Protein.
abstract: Described by our group a few years ago, the cholesteryl-ester transfer protein isoform (CETPI), exclusively expressed in the small intestine and present in human plasma, lacked a functional identification for a role of physiological relevance. Now, this study introduces CETPI as a new protein with the potential capability to recognise, bind and neutralise lipopolysaccharides (LPS). Peptides derived from the C-terminal domain of CETPI showed that CETPI not only might interact with several LPS serotypes but also might displace LPS bound to the surface of cells. Peptide VSAK, derived from the last 18 residues of CETPI, protected against the cytotoxic effect of LPS on macrophages. At high concentrations, when different cell types were tested in culture, it did not exhibit cytotoxicity by itself and it did prevent the expression of pro-inflammatory cytokines as well as the generation of oxidative stress conditions. In a rabbit model of septic shock, the infusion of peptide VSAK exerted a protective effect against the effects of LPS and reduced the presence of tumor necrosis factor-alpha (TNFα) in plasma. Therefore, CETPI is proposed as a new protein with the capability to advance the possibilities for better understanding and treatment of the dangerous effects of LPS in vivo.
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. 04510 México, D.F. México.|Facultad de Medicina, Universidad Autónoma de Baja California, Mexicali, 21000 Baja California, México.
authors.forename: Victor
authors.initials: V
authors.lastname: García-González
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. 04510 México, D.F. México.
authors.forename: Nadia
authors.initials: N
authors.lastname: Gutiérrez-Quintanar
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México. 04510 México, D.F. México.
authors.forename: Jaime
authors.initials: J
authors.lastname: Mas-Oliva
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D010455:Peptides / Q000378:metabolism; D010949:Plasma / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology*; D012772:Shock, Septic / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D016207:Cytokines; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010455:Peptides; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein