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Identification of two novel LPS-binding proteins in Kupffer cells: implications in TNF- production

Laboratory of Cancer Biology, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA, peterthomas{at}creighton.edu, Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska, USA

Donald A. Lazure

Laboratory of Cancer Biology, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

Runna Moussa

Laboratory of Cancer Biology, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

Olga Bajenova

Department of Surgery, Boston University School of Medicine, Boston, Massachusetts, USA, Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska, USA

Peter A. Burke

Department of Surgery, Boston University School of Medicine, Boston, Massachusetts, USA

Aniruddha Ganguly

Laboratory of Cancer Biology, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

R. Armour Forse

Department of Surgery, Boston University School of Medicine, Boston, Massachusetts, USA, Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska, USA

Using a combination of gel-exclusion chromatography and ligand binding with [¹²⁵I]-lipopolysaccharide (LPS), we discovered two novel endotoxin-binding proteins, p31^LPB and p34^LPB, in Kupffer cells. Their molecular masses suggest that these are previously undescribed LPS-binding proteins (LBPs). Evidence from detergent-based cell extractions shows that these proteins are probably transmembrane or located on the inner leaflet of the lipid bilayer. We have partially purified the proteins from detergent extracts of Kupffer cells and proven that they bind diphosphoryl lipid A, an interaction associated with TNF- production. The proteins do not bind monophosphoryl lipid A. Diphosphoryl lipid A binding occurs in the absence of serum, suggesting a mechanism of cytokine production distinct from that involving CD14 and lipopolysaccharide-binding protein (LPB). The two proteins were not detectable in resident peritoneal macrophages or in a number of other cell lines of the macrophage/monocyte lineage, suggesting specificity towards terminally differentiated macrophages such as Kupffer cells.

Key Words: LPS-binding proteins • endotoxin-binding proteins • Kupffer cells • liver

Journal of Endotoxin Research, Vol. 12, No. 6, 352-357 (2006)
DOI: 10.1177/09680519060120060501


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