title: Lipopolysaccharide needs soluble CD14 to interact with TLR4 in human monocytes depleted of membrane CD14.
abstract: Toll-like receptors recognize specific patterns of microbial components and regulate the activation of both innate and adaptive immunity. TLR4 recognizes lipopolysaccharide (LPS) in monocytes/macrophages with the help of other molecules like CD14 and MD-2, which indicates that the functional LPS receptor forms a large complex. The functional relationship between the components has been the subject of debate, as have the modifications induced by the ligand in the expression of some of these components. Moreover, as for other members of this family of receptors, the possible direct interaction of receptors and their ligands is a matter of discussion. In this paper we address the question of whether the expression of some of the components influences the expression of the rest. Human monocytes in which CD14 has been downregulated through interference in the turnover of the molecule at the Golgi level, show normal membrane TLR4 expression, when compared with control cells. On the other hand, LPS alters membrane TLR4 expression by monocytes devoid of membrane CD14 only in the presence of human serum. The effect of serum is blocked by anti-CD14 monoclonal antibodies, which strongly suggests a functional role for soluble CD14/LPS complexes in the interaction with TLR4. Our data add information on the relationship between the components of the LPS receptor and the characteristics of the interaction of LPS and TLR4 in cells devoid of membrane CD14.
authors.affiliation: Department of Immunology, Clínica Universitaria, Faculty of Medicine, University of Navarra, 31008 Pamplona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Moreno
authors.forename: Juana
authors.initials: J
authors.lastname: Merino
authors.forename: Natalia
authors.initials: N
authors.lastname: Ramírez
authors.forename: Aitziber
authors.initials: A
authors.lastname: Echeverría
authors.forename: Fernando
authors.initials: F
authors.lastname: Pastor
authors.forename: Alfonso
authors.initials: A
authors.lastname: Sánchez-Ibarrola
mesh_terms: D000328:Adult; D020126:Brefeldin A / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011500:Protein Synthesis Inhibitors; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D020126:Brefeldin A