title: MD-2 binds to bacterial lipopolysaccharide.
abstract: 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 from Salmonella minnesota and Escherichia coli in five different assays; one assay yielded an apparent KD of 65 nm. MD-2 binding to LPS did not require LPS-binding proteins LBP and CD14; in fact LBP competed with MD-2 for LPS. MD-2 enhanced the biological activity of LPS in toll-like receptor 4-transfected Chinese hamster ovary cells but inhibited LPS activation of U373 astrocytoma cells and of monocytes in human whole blood. These data indicate that MD-2 is a genuine LPS-binding protein and strongly suggest that MD-2 could play a role in regulation of cellular activation by LPS depending on its local availability.
authors.affiliation: Veterans Administration San Diego Healthcare System and Department of Pathology and Medicine, University of California San Diego, 92161, USA. sviriyak@ucsd.edu
authors.forename: S
authors.initials: S
authors.lastname: Viriyakosol
authors.forename: P S
authors.initials: PS
authors.lastname: Tobias
authors.forename: R L
authors.initials: RL
authors.lastname: Kitchens
authors.forename: T N
authors.initials: TN
authors.lastname: Kirkland
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D051218:Lymphocyte Antigen 96; D011485:Protein Binding
chemical_list: D000954:Antigens, Surface; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96