Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts

The glycosylphosphatidylinositol-anchored receptor CD14 plays a major role in the inflammatory response of monocytes to lipopolysaccharide. Here, we d escribe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting ce lls, CD14 was associated with CD55, the Fc gamma -receptors CD32 and CD64 a nd the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide in additi on, induced co-clustering with Toll-like receptor 4, Fc gamma -RIIIa (CD16a ) and the tetraspanin CD81 while CD47 was dissociated. The different recept or complexes may be linked to ligand-specific cellular responses initiated by CD14.