Histones: a novel class of lipopolysaccharide-binding molecules.
Unlike soluble and membrane forms of lipopolysaccharide (LPS)-binding proteins, intracellular LPS-binding molecules are poorly documented. We looked for such molecules in a murine lung epithelial cell line. Two proteins with LPS-binding activity were isolated and unambiguously identified as histones H2A.1 and H4 by mass spectrometry. Synthetic peptides representing partial structures indicated that the LPS binding site is located in the C-terminal moiety of the histones. Extending the study, we found that histones H1, H2A, H2B, H3, and H4 from calf thymus are all able to bind LPS. Bindings were specific, and affinities, determined by isothermal titration calorimetry, were (except for H4) higher than that of the LPS-binding antibiotic polymyxin B. In the presence of H2A the binding of LPS to the macrophage cell line RAW 264.7, and the LPS-induced production of TNF-alpha and nitric oxide by these cells, were markedly reduced. Histones may thus represent a new class of intracellular and extracellular LPS sensors.
Augusto
Luis A
LA
Endotoxin Group, UMR-8619 of the National Center for Scientific Research, University of Paris-Sud, 91405 Orsay, France.
Decottignies
Paulette
P
Synguelakis
Monique
M
Nicaise
Magali
M
Le Maréchal
Pierre
P
Chaby
Richard
R
D000209:Acute-Phase Proteins; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004847:Epithelial Cells / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D013058:Mass Spectrometry; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011112:Polymyxin B / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D006657:Histones; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009569:Nitric Oxide; D010446:Peptide Fragments; D011112:Polymyxin B; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein