Phosphatidylinositides bind to plasma membrane CD14 and can prevent monocyte activation by bacterial lipopolysaccharide.
Although bacterial lipopolysaccharides (LPS) and several other microbial agonists can bind to mCD14 (membrane CD14), a cell-surface receptor found principally on monocytes and neutrophils, host-derived mCD14 ligands are poorly defined. We report here that phosphatidylinositol (PtdIns), phosphatidylinositol-4-phosphate, and other phosphatidylinositides can bind to mCD14. Phosphatidylserine (PS), another anionic glycerophospholipid, binds to mCD14 with lower apparent affinity than does PtdIns. LPS-binding protein, a lipid transfer protein found in serum, facilitates both PS- and PtdIns-mCD14 binding. PtdIns binding to mCD14 can be blocked by anti-CD14 monoclonal antibodies that inhibit LPS-mCD14 binding, and PtdIns can inhibit both LPS-mCD14 binding and LPS-induced responses in monocytes. Serum-equilibrated PtdIns also binds to mCD14-expressing cells, raising the possibility that endogenous PtdIns may modulate cellular responses to LPS and other mCD14 ligands in vivo.
Wang
P Y
PY
Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9113, USA.
Kitchens
R L
RL
Munford
R S
RS
D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004926:Escherichia coli; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism* / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C037178:phosphatidylinositol 4-phosphate