Oxidized Phospholipid, 1-Palmitoyl-2-(9′-Oxo-Nonanoyl)-Glycerophosphocholine (PON-GPC), Produced in the Lung Due to Cigarette Smoking, Impairs Immune Function in Macrophages

Kimura, Tomomi; Shibata, Yoko; Yamauchi, Keiko; Igarashi, Akira; Inoue, Sumito; Abe, Shuichi; Fujita, Kazuhiro; Uosaki, Yoichi

doi:10.1007/s00408-011-9331-2

Cited by 14 publications

(25 citation statements)

References 43 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Together with that information and high-resolution MS/MS data, the most likely molecule within an error lower than 10 ppm would be the oxidized phospholipid 1-hexadecanoyl-2-(9-oxononanoyl)- sn -glycero-3-phosphoethanolamine (Figure 5). Its phosphatidylcholine analogue has been reported as a product of lung surfactant phospholipid oxidation in smokers, 41 and some oxidized ethanolamine phospholipids have also been described as ozonolysis products in bronchoalveolar lavage. 42 Although in this case the MS/MS data of the natural occurring metabolite and its isotopologue were not added to the databases due to the lack of complementary information to accurately define the position of the carbonyl within the fatty acid chain, the use of isotope-labeled microorganisms, together with other METLIN tools available, provides a good estimation for the characterization of this unknown natural product synthesized by these microorganisms.…”

Section: Resultsmentioning

confidence: 99%

METLIN: A Technology Platform for Identifying Knowns and Unknowns

Guijas¹,

et al. 2018

View full text Add to dashboard Cite

METLIN originated as a database to characterize known metabolites and has since expanded into a technology platform for the identification of known and unknown metabolites and other chemical entities. Through this effort it has become a comprehensive resource containing over 1 million molecules including lipids, amino acids, carbohydrates, toxins, small peptides, and natural products, among other classes. METLIN’s high-resolution tandem mass spectrometry (MS/MS) database, which plays a key role in the identification process, has data generated from both reference standards and their labeled stable isotope analogues, facilitated by METLIN-guided analysis of isotope-labeled microorganisms. The MS/MS data, coupled with the fragment similarity search function, expand the tool’s capabilities into the identification of unknowns. Fragment similarity search is performed independent of the precursor mass, relying solely on the fragment ions to identify similar structures within the database. Stable isotope data also facilitate characterization by coupling the similarity search output with the isotopic m/z shifts. Examples of both are demonstrated here with the characterization of four previously unknown metabolites. METLIN also now features in silico MS/MS data, which has been made possible through the creation of algorithms trained on METLIN’s MS/MS data from both standards and their isotope analogues. With these informatic and experimental data features, METLIN is being designed to address the characterization of known and unknown molecules.

show abstract

Section: Resultsmentioning

confidence: 99%

METLIN: A Technology Platform for Identifying Knowns and Unknowns

Guijas¹,

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Peroxidation of phospholipids, such as PAPC, leads to generation of OX-PAPC, which consists of a mixture of truncated oxidized phospholipids (Ox-PLs) such as POVPC, PGPC and PazPC and different types of low molecular weight aldehydes (e.g.4-HNE, MDA) [14]. Levels of Ox-PLs, 4-HNE, and MDA are elevated in lungs of mice exposed to CS [15,16,17] and in COPD patients [18]. Additionally, reactive oxygen species generated at the site of inflammation due to NADPH oxidase and myeloperoxidase activity of phagocytes also mediate peroxidation of lipids and elevate Ox-PLs [19,20].…”

Section: Introductionmentioning

confidence: 99%

Oxidized phospholipids impair pulmonary antibacterial defenses: Evidence in mice exposed to cigarette smoke

Thimmulappa

Xing

Kim

et al. 2012

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Patients with COPD are associated with poor pulmonary anti-bacterial innate defenses, which increase the risk for frequent acute exacerbations caused by bacterial infection. Despite elevated numbers of phagocytes (macrophages and neutrophils), airways of patients with COPD show stable bacterial colonization. A defect in the phagocytic ability of alveolar macrophages (AMs) is one of the primary reasons for failure to clear the invading bacteria in airways of smokers and COPD patients and also in mice exposed to cigarette smoke (CS). Oxidative stress, as a result of CS exposure is implicated; however, the factors or mediators that inhibit phagocytic activity of AMs in lungs of smokers remain unclear. In the current study, we provide evidence that accumulation of oxidized phospholipids (Ox-PLs) mediate inhibition of phagocytic function of AMs in CS-exposed mice. Mice exposed to 6 months of CS showed impaired bacterial phagocytosis and clearance by AMs and elevated levels of Ox-PLs in bronchoalveolar lavage fluid (BALF), compared to mice exposed to room air. Intratracheal instillation of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OX-PAPC) inhibited phagocytic activity of AMs and impaired pulmonary bacterial clearance in mice. In vitro studies demonstrated that exposure of J774 macrophages to OX-PAPC inhibited bacterial phagocytosis and clearance. However, pre-treatment of OX-PAPC with the monoclonal antibody EO6, which specifically binds to oxidized phospholipid but not native phospholipid, abolished OX-PAPC induced inhibition of bacterial phagocytosis and clearance. Incubation of BALF retrieved from CS-exposed mice impaired bacterial phagocytosis by J774 macrophages, which was abolished by pre-treatment of BALF with the EO6 antibody. In conclusion, our study shows that Ox-PLs generated following chronic CS exposure could play a crucial role in inhibiting phagocytic function of AMs and thus impair pulmonary anti-bacterial innate defenses in CS-exposed mice. Therapeutic approaches that augment pulmonary antioxidant defenses could be beneficial in reducing oxidative stress-driven impairment of phagocytosis by AMs in smokers and COPD patients.

show abstract

“…38 Furthermore, the toxicity of 16:0/9al-PC was addressed in this study using a trypan blue exclusion assay and it was found that 88% of the macrophages were alive after treatment with the oxidized lipid for one hour, which correlates with a previous study which found that the viability of macrophages was not affected by treatment with 16:0/9al-PC (up to 40 µM). 8 …”

Section: Discussionmentioning

confidence: 99%

“…In order to assess toxicity, a trypan blue exclusion assay was performed and 88% of the RPM were alive after 1 hour of treatment with 37.5 µM 16:0/9al-PC, which was similar to the cell viability results of RAW 264.7 cells exposed to 16:0/9al-PC. 8 …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Phospholipid Ozonation Products Activate the 5-Lipoxygenase Pathway in Macrophages

Berry

Murphy

2016

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Ozone is a highly reactive environmental toxicant that can react with the double bonds of lipids in pulmonary surfactant. This study was undertaken to investigate the proinflammatory properties of the major lipid-ozone product in pulmonary surfactant, 1-palmitoyl-2-(9’-oxo-nonanoyl)-glycerophosphocholine (16:0/9al-PC), with respect to eicosanoid production. A dose-dependent increase in the formation of 5-lipoxygenase (5-LO) products was observed in murine resident peritoneal macrophages (RPM) and alveolar macrophages (AM) upon treatment with 16:0/9al-PC. In contrast, the production of cyclooxygenase (COX) derived eicosanoids did not change from basal levels in the presence of 16:0/9al-PC. When 16:0/9al-PC and the TLR2 ligand, zymosan, were added to RPM or AM, an enhancement of 5-LO product formation along with a concomitant decrease in COX product formation was observed. Neither intracellular calcium levels or arachidonic acid release were influenced by the addition of 16:0/9al-PC to RPM. Results from mitogen-activated protein kinase (MAPK) inhibitor studies and direct measurement of phosphorylation of MAPKs revealed that 16:0/9al-PC activates the p38 MAPK pathway in RPM, which results in activation of 5-LO. Our results indicate that 16:0/9al-PC has a profound effect on the eicosanoid pathway, which may have implications in inflammatory pulmonary disease states where eicosanoids have been shown to play a role.

show abstract

Oxidized Phospholipid, 1-Palmitoyl-2-(9′-Oxo-Nonanoyl)-Glycerophosphocholine (PON-GPC), Produced in the Lung Due to Cigarette Smoking, Impairs Immune Function in Macrophages

Abstract: CS may attenuate innate immunity in the lungs through oxidization of surfactant phospholipids.

Cited by 14 publications

References 43 publications

METLIN: A Technology Platform for Identifying Knowns and Unknowns

METLIN: A Technology Platform for Identifying Knowns and Unknowns

Oxidized phospholipids impair pulmonary antibacterial defenses: Evidence in mice exposed to cigarette smoke

Phospholipid Ozonation Products Activate the 5-Lipoxygenase Pathway in Macrophages

Contact Info

Product

Resources

About