Akashi S, Ogata H, Kirikae F, Kirikae T, Kawasaki K, Nishijima M, Shimazu R, Nagai Y, Fukudome K, Kimoto M, Miyake K
Department of Immunology, Saga Medical School, Saga, Nabeshima, Japan.
Biochem Biophys Res Commun. 2000 Feb 5;268(1):172-7. doi: 10.1006/bbrc.2000.2089.
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.
Toll样受体4（TLR4）与相关的MD-2组成的复合物在细胞系中表达时可识别脂多糖（LPS）的存在。我们在此表明，正常人单核细胞表达TLR4并通过TLR4对LPS进行信号传导。CD14是一种与LPS结合并促进其信号传导的分子。然而，关于CD14与TLR4-MD-2的关系却知之甚少。我们发现CD14有助于TLR4-MD-2感知并传导LPS的存在。CD14也参与了凋亡细胞的识别，这会导致在无激活情况下的吞噬作用。膜磷脂如磷脂酰丝氨酸（PS）或磷脂酰肌醇（PtdIns）被认为是凋亡细胞中CD14的配体。我们发现PtdIns在通过TLR4-MD-2的信号传导中作为LPS拮抗剂。TLR4-MD-2似乎能区分LPS和磷脂。因此，通过TLR4-MD-2的信号传导受CD14和磷脂如PtdIns的调节。
