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 describe that ceramide, a constituent of atherogenic lipoproteins, binds to CD14 and induces clustering of CD14 to co-receptors in rafts. In resting cells, CD14 was associated with CD55, the Fcgamma-receptors CD32 and CD64 and the pentaspan CD47. Ceramide further recruited the complement receptor 3 (CD11b/CD18) and CD36 into proximity of CD14. Lipopolysaccharide, in addition, induced co-clustering with Toll-like receptor 4, Fcgamma-RIIIa (CD16a) and the tetraspanin CD81 while CD47 was dissociated. The different receptor complexes may be linked to ligand-specific cellular responses initiated by CD14.
Pfeiffer
A
A
Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany.
Böttcher
A
A
Orsó
E
E
Kapinsky
M
M
Nagy
P
P
Bodnár
A
A
Spreitzer
I
I
Liebisch
G
G
Drobnik
W
W
Gempel
K
K
Horn
M
M
Holmer
S
S
Hartung
T
T
Multhoff
G
G
Schütz
G
G
Schindler
H
H
Ulmer
A J
AJ
Heine
H
H
Stelter
F
F
Schütt
C
C
Rothe
G
G
Szöllôsi
J
J
Damjanovich
S
S
Schmitz
G
G
D015703:Antigens, CD / Q000378:metabolism; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D029721:Drosophila Proteins; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism*; D008565:Membrane Proteins; D009000:Monocytes / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D060225:Tetraspanin 28; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D015703:Antigens, CD; D051928:CD47 Antigen; C497894:CD47 protein, human; C554798:CD81 protein, human; D002352:Carrier Proteins; D002518:Ceramides; D029721:Drosophila Proteins; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D060225:Tetraspanin 28; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors