LPS-dependent interaction of Mac-2-binding protein with immobilized CD14.
CD14 is a glycosylphosphatidyl-inositol (GPI)-linked, 55 kDa protein that binds bacterial lipopolysaccharide (LPS, endotoxin) and plays a key role in mediating cellular responses to this potent inflammatory stimulus. Binding of LPS to CD14 is facilitated by serum proteins such as LPS binding protein (LBP). To determine if there are additional plasma proteins that bind to CD14, plasma was passed over immobilized CD14 in the presence or absence of LPS, and retained proteins were eluted. This procedure isolated not only LBP but also a serum protein known as Mac-2-binding protein (Mac-2-BP), a 97 kDa species without a known function. Binding of both LBP and Mac-2-BP to CD14 required the simultaneous presence of LPS. Experiments with purified Mac-2-BP showed that this protein alone neither enabled responses of CD14-bearing cells to LPS nor blocked the ability of plasma to enable responses of CD14-bearing cells to LPS. However, Mac-2-BP did slow the neutralization of LPS mediated by plasma lipoprotein. These studies describe the first potential function for Mac-2-BP, and suggest that neutralization of LPS in plasma may be controlled by proteins in addition to LBP and CD14.
Yu
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Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021, USA.
Wright
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D000209:Acute-Phase Proteins; D000818:Animals; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D016466:CHO Cells; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D002846:Chromatography, Affinity; D006224:Cricetinae; D006023:Glycoproteins / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D008895:Milk, Human / Q000737:chemistry; D012475:Salmonella; D000099231:Lipopolysaccharide-Binding Protein; D016326:Extracellular Matrix Proteins
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins