Phosphatidylinositides Bind to Plasma Membrane CD14 and Can Prevent Monocyte Activation by Bacterial Lipopolysaccharide

Wang, Ping-yuan; Kitchens, Richard L.; Munford, Robert S.

doi:10.1074/jbc.273.38.24309

Cited by 89 publications

(68 citation statements)

References 34 publications

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“…Previous studies have provided evidence that the antagonism of LPS activation through LBP/CD14/MD2/TLR4 is dependent upon the molecular class and species of phospholipid used as an antagonist (17)(18)(19)(20). We examined the molecular specificity of the POPG effect on RSV-elicited cytokine production by comparing the effects of POPG with a phospholipid counterpart containing a choline polar moiety, palmitoyl-oleoylphosphatidylcholine (POPC).…”

Section: Popg Specifically Attenuates Proinflammatory Cytokine Producmentioning

confidence: 99%

“…Additional studies have identified phosphatidylglycerol (PG) as an antagonist of LPS binding protein (LBP), and CD14 (18)(19)(20). Although PG constitutes about 10% of surfactant phospholipids, the high concentration of lipid in the extracellular surfactant layer within the alveolus, results in PG levels as high as 3.5 mg/mL This extraordinary level of PG is not found in any other tissue or mucosal surface in mammals.…”

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confidence: 99%

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Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus–induced inflammation and infection

Numata

Chu

Dakhama

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

158

244

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Respiratory syncytial virus (RSV) is the most common cause of hospitalization for respiratory tract infection in young children. It is also a significant cause of morbidity and mortality in elderly individuals and in persons with asthma and chronic obstructive pulmonary disease. Currently, no reliable vaccine or simple RSV antiviral therapy is available. Recently, we determined that the minor pulmonary surfactant phospholipid, palmitoyl-oleoyl-phosphatidylglycerol (POPG), could markedly attenuate inflammatory responses induced by lipopolysaccharide through direct interactions with the Toll-like receptor 4 (TLR4) interacting proteins CD14 and MD-2. CD14 and TLR4 have been implicated in the host response to RSV. Treatment of bronchial epithelial cells with POPG significantly inhibited interleukin-6 and -8 production, as well as the cytopathic effects induced by RSV. The phospholipid bound RSV with high affinity and inhibited viral attachment to HEp2 cells. POPG blocked viral plaque formation in vitro by 4 log units, and markedly suppressed the expansion of plaques from cells preinfected with the virus. Administration of POPG to mice, concomitant with viral infection, almost completely eliminated the recovery of virus from the lungs at 3 and 5 days after infection, and abrogated IFN-γ (IFN-γ) production and the enhanced expression of surfactant protein D (SP-D). These findings demonstrate an important approach to prevention and treatment of RSV infections using exogenous administration of a specific surfactant phospholipid.antiviral | innate immunity | respiratory epithelium R espiratory syncytial virus (RSV) is an important pathogen that infects 98% of children within the first 2 years of life, and also causes serious disease in elderly individuals and persons with chronic lung disease. In the 1980s, an estimated 100,000 children were hospitalized annually with RSV infection in the United States (1). Although RSV is commonly considered a pediatric disease, it is also highlighted as an opportunistic pathogen (2), with infections producing a mortality rate of 30-100% in immunosuppressed individuals (1). There is growing appreciation that RSV is an important pathogen in elderly and high-risk patients, and a cause of acute exacerbations of asthma (3, 4) and chronic obstructive pulmonary disease (COPD) (5). Over the period 1999-2003, RSV was responsible for hospitalization rates of 10.6% for pneumonia, 11.4% for COPD, 5.4% for congestive heart failure, and 7.2% for asthma (6).No vaccine is currently available for prevention of RSV infection. Several vaccine candidates have not only proved to be ineffective, but have also been shown to lead to vaccine-enhanced disease (7,8). Inhibitors directed against the RSV fusion protein (F protein) were abandoned partly because of the frequency of resistant mutations mapping to the F gene (9). A monoclonal antibody against F protein, Palivizumab, has restricted application and it is recommended for prophylactic use during the RSV season, for high-risk infants (1). Currently the onl...

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Section: Popg Specifically Attenuates Proinflammatory Cytokine Producmentioning

confidence: 99%

mentioning

confidence: 99%

Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus–induced inflammation and infection

Numata

Chu

Dakhama

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

158

244

View full text Add to dashboard Cite

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“…But the multifunctionality of CD14 is underscored by its role in apoptotic cell clearance when it induces an opposite macrophage response (Devitt et al 1998, Gregory 2000. In spite of binding to phospholipids, including PS (Wang et al 1998), it seems unlikely that CD14 can function as a PS receptor, at least when judged by in vitro assays of the engulfment ability of inactivated macrophages (Devitt et al 2003). By contrast, a putative candidate for CD14 recognition on apoptotic cell surface is the highly glycosylated Ig-superfamily member, the Intercellular adhesion molecule 3 (ICAM-3), constitutively expressed on leukocytes (Fawcett et al 1992).…”

Section: Apoptotic Cell Recognition In Mammalian Systems: Redundancymentioning

confidence: 99%

Apoptotic cell and phagocyte interplay: recognition and consequences in different cell systems

Moreira

Barcinski

2004

An. Acad. Bras. Ciênc.

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Cell death by apoptosis is characterized by specific biochemical changes, including the exposure of multiple ligands, expected to tag the dying cell for prompt recognition by phagocytes. In non-pathological conditions, an efficient clearance is assured by the redundant interaction between apoptotic cell ligands and multiple receptor molecules present on the engulfing cell surface. This review concentrates on the molecular interactions operating in mammalian and non-mammalian systems for apoptotic cell recognition, as well as on the consequences of their signaling. Furthermore, some cellular models where the exposure of the phosphatidylserine (PS) phospholipid, a classical hallmark of the apoptotic phenotype, is not followed by cell death will be discussed.

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“…Work from our laboratory 8,10,24 and elsewhere 25 has shown that human and murine macrophages utilise plasma membrane-anchored CD14 (mCD14) in apoptotic-cell clearance. In view of CD14's established capacity to interact with phospholipids, [26][27][28][29] we reasoned that CD14 might function as a PS-receptor for apoptotic cells. 10 We now report, however, that CD14 does not function preferentially as a PS-receptor in apoptotic-cell clearance, supporting the PS-R's principal role in this regard.…”

Section: Introductionmentioning

confidence: 99%

CD14-dependent clearance of apoptotic cells by human macrophages: the role of phosphatidylserine

et al. 2003

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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 membraneanchored 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.

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Phosphatidylinositides Bind to Plasma Membrane CD14 and Can Prevent Monocyte Activation by Bacterial Lipopolysaccharide

Cited by 89 publications

References 34 publications

Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus–induced inflammation and infection

Pulmonary surfactant phosphatidylglycerol inhibits respiratory syncytial virus–induced inflammation and infection

Apoptotic cell and phagocyte interplay: recognition and consequences in different cell systems

CD14-dependent clearance of apoptotic cells by human macrophages: the role of phosphatidylserine

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