CD14-dependent clearance of apoptotic cells by human macrophages: the role of phosphatidylserine.
Apoptotic-cell clearance is dependent on several macrophage surface molecules, including CD14. Phosphatidylserine (PS) becomes externalised during apoptosis and participates in the clearance process through its ability to bind to a novel receptor, PS-R. CD14 has the proven ability to bind phospholipids and may function as an alternative receptor for the externalised PS of apoptotic cells. Here we demonstrate that CD14 does not function preferentially as a PS receptor in apoptotic-cell clearance. Compared with phosphatidylcholine and phosphatidylethanolamine, PS was the least active phospholipid binding to human monocyte-derived macrophages and showed no specificity for soluble or membrane-anchored CD14. Significantly, PS-containing liposomes failed to inhibit CD14-dependent uptake of apoptotic cells by macrophages. PS exposure was, however, found to be insufficient for either CD14-dependent or CD14-independent apoptotic-cell uptake by phagocytes. The additional features that enable apoptotic-cell clearance are derived from mechanisms that can be divorced temporally from those responsible for the morphological features of apoptosis.
Devitt
A
A
MRC Center for Inflammation Research, University of Edinburgh, UK.
Pierce
S
S
Oldreive
C
C
Shingler
W H
WH
Gregory
C D
CD
D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D050356:Lipid Metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism / Q000502:physiology*; D008081:Liposomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*; D011485:Protein Binding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014466:Ultraviolet Rays
D017304:Annexin A5; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008081:Liposomes; D010718:Phosphatidylserines; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D003513:Cycloheximide