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Phosphatidylinositides bind to plasma membrane CD14 and can prevent monocyte activation by bacterial
P Y Wang1, R L Kitchens, R S Munford
1Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9113, USA.
Abstract:
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.
Insights
Host-derived phosphatidylinositol (PtdIns) binds to membrane CD14 (mCD14), a receptor on immune cells. This binding can influence cellular responses to bacterial lipopolysaccharides (LPS).
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Membrane CD14 (mCD14) is a cell-surface receptor primarily on monocytes and neutrophils.
- While mCD14 binds microbial agonists like bacterial lipopolysaccharides (LPS), host-derived ligands are not well understood.
Purpose of the Study:
- To identify host-derived ligands that bind to mCD14.
- To investigate the functional implications of phosphatidylinositol binding to mCD14.
Main Methods:
- Binding assays were performed to assess the interaction of various phosphatidylinositides and phosphatidylserine (PS) with mCD14.
- The role of LPS-binding protein in facilitating these interactions was examined.
- Monoclonal antibodies were used to block PtdIns-mCD14 binding and assess its effect on LPS binding and LPS-induced monocyte responses.
Main Results:
- Phosphatidylinositol (PtdIns) and other phosphatidylinositides bind to mCD14.
- Phosphatidylserine (PS) also binds mCD14, but with lower affinity than PtdIns.
- LPS-binding protein enhances both PS and PtdIns binding to mCD14.
- PtdIns binding inhibits LPS binding to mCD14 and reduces LPS-induced monocyte activation.
- Serum-equilibrated PtdIns binds to mCD14-expressing cells.
Conclusions:
- Phosphatidylinositol (PtdIns) is identified as a host-derived ligand for membrane CD14 (mCD14).
- PtdIns binding to mCD14 can modulate cellular responses to bacterial lipopolysaccharides (LPS).
- Endogenous PtdIns may play a role in regulating immune cell responses in vivo.