Lipopolysaccharide (LPS) signal transduction and clearance. Dual roles for LPS binding protein and membrane CD14.
Under physiological conditions, lipopolysaccharide (LPS) activation of cells involves the LPS binding protein (LBP) and either membrane or soluble CD14. We find LPS forms a ternary complex with LBP and membrane CD14 (mCD14). Subsequent to complex formation and distinct from signal transduction, LBP and LPS internalize. Internalization can be separated from signal transduction with the anti-LBP antibody 18G4 and the anti-CD14 antibody 18E12. 18G4 inhibits LBP binding to mCD14 without blocking signal transduction or LPS transfer to soluble CD14; 18E12 inhibits signal transduction without affecting LPS binding and uptake. These data show that while LPS signal transduction and LPS clearance utilize both LBP and mCD14, the pathways bifurcate after LPS binding to mCD14.
Gegner
J A
JA
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Ulevitch
R J
RJ
Tobias
P S
PS
D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000378:metabolism*; D016466:CHO Cells; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D006224:Cricetinae; D004926:Escherichia coli; D006801:Humans; D007700:Kinetics; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D008961:Models, Structural; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D012475:Salmonella; D015398:Signal Transduction; D014162:Transfection; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000906:Antibodies; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D000099231:Lipopolysaccharide-Binding Protein