Regulatory Roles for CD14 and Phosphatidylinositol in the Signaling via Toll-like Receptor 4-MD-2

The complex consisting of Toll-like receptor 4 (TLR4) and associated MD-2 signals the presence of lipopolysaccharide (LPS) when it is expressed in cell lines. We here show that normal human mononuclear cells express TLR4 and signal LPS via TLR4. CD14 is a molecule that binds to LPS and facilitates i...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2000-02, Vol.268 (1), p.172-177
Main Authors: Akashi, Sachiko, Ogata, Hirotaka, Kirikae, Fumiko, Kirikae, Teruo, Kawasaki, Kiyoshi, Nishijima, Masahiro, Shimazu, Rintaro, Nagai, Yoshinori, Fukudome, Kenji, Kimoto, Masao, Miyake, Kensuke
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal
B-Lymphocytes - drug effects
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
Cell Line
Drosophila Proteins
Humans
Lipopolysaccharide Receptors - metabolism
Lipopolysaccharides - pharmacology
Membrane Glycoproteins - antagonists & inhibitors
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Mice
Monocytes - drug effects
Monocytes - immunology
Monocytes - metabolism
Phosphatidylinositols - metabolism
Receptors, Cell Surface - antagonists & inhibitors
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Signal Transduction
Toll-Like Receptor 4
Toll-Like Receptors
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The complex consisting of Toll-like receptor 4 (TLR4) and associated MD-2 signals the presence of lipopolysaccharide (LPS) when it is expressed in cell lines. We here show that normal human mononuclear cells express TLR4 and signal LPS via TLR4. CD14 is a molecule that binds to LPS and facilitates its signaling. Little is known, however, about the relationship of CD14 with TLR4-MD-2. We show that CD14 helps TLR4-MD-2 to sense and signal the presence of LPS. CD14 has also been implicated in recognition of apoptotic cells, which leads to phagocytosis without activation. Membrane phospholipids such as phosphatidylserine (PS) or phosphatidylinositol (PtdIns) are thought to serve as the ligands for CD14 in apoptotic cells. We find that PtdIns acts as an LPS antagonist in the signaling via TLR4-MD-2. TLR4-MD-2 seems to discriminate LPS from phospholipids. The signaling via TLR4-MD-2 is thus regulated by CD14 and phospholipid such as PtdIns.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2000.2089