Glycerophospholipids represent a common class of lipids critically important for integrity of cellular membranes. Oxidation of esterified unsaturated fatty acids dramatically changes biological activities of phospholipids. Apart from impairment of their structural function, oxidation makes oxidized phospholipids (OxPLs) markers of “modified-self” type that are recognized by soluble and cell-associated receptors of innate immunity, including scavenger receptors, natural (germ line-encoded) antibodies, and C-reactive protein, thus directing removal of senescent and apoptotic cells or oxidized lipoproteins. In addition, OxPLs acquire novel biological activities not characteristic of their unoxidized precursors, including the ability to regulate innate and adaptive immune responses. Effects of OxPLs described in vitro and in vivo suggest their potential relevance in different pathologies, including atherosclerosis, acute inflammation, lung injury, and many other conditions. This review summarizes cur...

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Generation and Biological Activities of Oxidized Phospholipids

Ions formed from lipids during electrospray ionization of crude lipid extracts have been mass-selected within a quadrupole linear ion trap mass spectrometer and allowed to react with ozone vapor. Gas-phase ion−molecule reactions between unsaturated lipid ions and ozone are found to yield two primary product ions for each carbon−carbon double bond within the molecule. The mass-to-charge ratios of these chemically induced fragments are diagnostic of the position of unsaturation within the precursor ion. This novel analytical technique, dubbed ozone-induced dissociation (OzID), can be applied both in series and in parallel with conventional collision-induced dissociation (CID) to provide near-complete structural assignment of unknown lipids within complex mixtures without prior fractionation or derivatization. In this study, OzID is applied to a suite of complex lipid extracts from sources including human lens, bovine kidney, and commercial olive oil, thus demonstrating the technique to be applicable to a br...

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Ozone-induced dissociation: elucidation of double bond position within mass-selected lipid ions.

B. Hydroxy Fatty Acids 484 C. Other Oxygenated Fatty Acids 486 1. Oxy-Fatty Acid 486 2. Hydroperoxy Fatty Acids 487 3. Expoxy Fatty Acids 487 4. Nitrated Fatty Acids 488 D. Eicosanoids 488 1. Prostaglandins 488 2. Leukotrienes 489 3. Lipoxins 491 4. Isoprostanes 492 III. Steroids 494 A. Neutral Steroids 495 B. Steroid Conjugates 495 C. Bile Acids 498 IV. Fat-Soluble Vitamins 499 A. Vitamin A 499 B. Vitamin D 499 C. Vitamin E and Carotenoids 500 D. Vitamin K 501 V. Complex Glycerolipids 501 A. Monoand Diglycerides 502 B. Triacylglycerols 502 C. Glycerophospholipids 505 1. Platelet Activating Factor 509 2. Plasmalogen Phospholipids 509 3. Lysophospholipids 509 4. Oxidized and Covalently Modified Phospholipids 511

Analysis of Nonvolatile Lipids by Mass Spectrometry

Mechanisms of radical formation from reactions of ozone with target molecules in the lung.

Asthma has a high prevalence in the United States, and persons with asthma may be at added risk from the adverse effects of hazardous air pollutants (HAPs) Complex mixtures (fine particulate matter and tobacco smoke) have been associated with respiratory symptoms and hospital admissions for asthma The toxic ingredients of these mixtures are HAPs, but whether ambient HAP exposures can induce asthma remains unclear Certain HAPs are occupational asthmagens, whereas others may act as adjuncts during sensitization HAPs may exacerbate asthma because, once sensitized, individuals can respond to remarkably low concentrations, and irritants lower the bronchoconstrictive threshold to respiratory antigens Adverse responses after ambient exposures to complex mixtures often occur at concentrations below those producing effects in controlled human exposures to a single compound In addition, certain HAPs that have been associated with asthma in occupational settings may interact with criteria pollutants in ambient air to exacerbate asthma Based on these observations and past experience with 188 HAPs, a list of 19 compounds that could have the highest impact on the induction or exacerbation of asthma was developed Nine additional compounds were identified that might exacerbate asthma based on their irritancy, respirability, or ability to react with biological macromolecules Although the ambient levels of these 28 compounds are largely unknown, estimated exposures from emissions inventories and limited air monitoring suggest that aldehydes (especially acrolein and formaldehyde) and metals (especially nickel and chromium compounds) may have possible health risk indices sufficient for additional attention Recommendations for research are presented regarding exposure monitoring and evaluation of biologic mechanisms controlling how these substances induce and exacerbate asthma

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Hazardous Air Pollutants and Asthma

While considerable effort has been expended on determining the health effects of exposure to typical urban concentrations of O3, little is known about the chemical events responsible for toxicity. Phospholipids containing unsaturated fatty acids in the cell membranes of lung cells are likely reaction sites for inhaled ozone (O3). In this study, we examined the reaction of O3 with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) in unilamellar phospholipid vesicles. Reaction of ozone with the carbon-carbon double bond of POPC yielded an aldehyde and a hydroxy hydroperoxide. The hydroxy hydroperoxide eliminated H2O2 to yield a second aldehyde. Upon further ozonolysis, the aldehydes were oxidized to the corresponding carboxylic acids. A material balance showed that no other reaction consumed POPC and O3 or produced these products. As a mechanistic probe, we measured incorporation of oxygen-18 from 18O3 into aldehyde, carboxylic acid, and H2O2. Approximately 50% of the aldehyde oxygen atoms were derived from O3. Oxygen in H2O2 was derived solely from O3, where both oxygen atoms in a molecule of H2O2 were from the same molecule of O3. One of the carboxylic acid oxygen atoms was derived from the precursor aldehyde, while the other was derived from O3. These results support the following mechanism. Cleavage of the carbon-carbon double bond of POPC by O3 yields a carbonyl oxide and an aldehyde. Reaction of H2O with the carbonyl oxide yields a hydroxy hydroperoxide, preventing formation ozonide by reaction of the carbonyl oxide and aldehyde. Elimination of H2O2 from the hydroxy hydroperoxide yields a second aldehyde. Oxidation of the aldehydes by O3 yields carboxylic acids.

Products and mechanism of the reaction of ozone with phospholipids in unilamellar phospholipid vesicles

A prototype fire suppression system was tested in one full-scale vehicle crash tests and three static vehicle fire tests. The prototype fire suppression system consisted of 2 Solid Propellant Gas Generators and two optical detectors. These components were installed on the hood of the test vehicle. A vehicle crash test and a series of static vehicle fire tests were performed to determine the effectiveness of this prototype fire suppression systems in extinguishing fires in the engine compartment of a crashed vehicle.

Evaluation of Automatic Fire Suppression Systems in Full Scale Vehicle Fire Tests and Static Vehicle Fire Tests

Five human subjects were exposed to an atmosphere containing 200 ppm of methanol in a test chamber for 7 hours per day for 5 consecutive days (Monday through Friday). Ambient air in the chamber was monitored continuously for methanol, while urine was monitored for methanol and formic acid. Spot urine specimens were collected immediately before and immediately after exposure periods on Monday through Friday, and also on the Saturday and Sunday mornings following the week of exposure. Morning urine specimens obtained Tuesday through Saturday were collected approximately 16 hours following cessation of exposure on the preceding day. Mean urinary methanol concentrations were increased from baseline at the end of each exposure session (Monday through Friday), but had returned to baseline in samples collected 16 hours following cessation of exposure. The concentration of formic acid in morning urine specimens did not change significantly over the 7 days of this experiment. These results indicate that: ...

Absence of Formic Acid Accumulation in Urine Following Five Days of Methanol Exposure

Analysis of Reservoir Pressure Decay, Velocity and Concentrations Fields of Natural Gas Venting from Pressurized Reservoir into the Atmosphere

An evaluation methodology has been developed for assessing the suitability of R-1234yf in vehicles. This relates primarily to evaluating the flammability of R-1234yf in the engine compartment during a frontal collision. This paper will discuss the process followed in the methodology, the technical rationale for this process, and the results of the analysis. The specific types of analysis included in the methodology are: exhaust-system thermal characterization, computer simulated crash tests, actual crash tests, teardown and examination of crashed parts, and releases of refrigerant onto hot exhaust manifolds. Each type of analysis was logically ordered and combined to produce a comprehensive evaluation methodology. This methodology has been applied and demonstrates that R-1234yf is difficult to ignite when factors that occur in frontal crashes are simultaneously considered. Factors considered in this analysis include: crush and deformation of the vehicle structure, airflow in the engine compartment, exhaust system temperatures during different driving scenarios, and coolant release due to damage of the engine coolant system. Such findings support the conclusion of the Society of Automotive Engineers Cooperative Research Team (SAE CRP1234-4) regarding R-1234yf usage: "risks are still very small compared to the risks of a vehicle fire from all causes and well below risks that are commonly viewed as acceptable by the general public." This methodology can provide a representative and more realistic assessment of the suitability of R-1234yf in automotive air-conditioning systems. The evaluation methodology can be applied to any vehicle. Language: en

Jeffrey Santrock

Papers

Products and mechanism of the reaction of ozone with phospholipids in unilamellar phospholipid vesicles

Evaluation of Automatic Fire Suppression Systems in Full Scale Vehicle Fire Tests and Static Vehicle Fire Tests

Absence of Formic Acid Accumulation in Urine Following Five Days of Methanol Exposure

Analysis of Reservoir Pressure Decay, Velocity and Concentrations Fields of Natural Gas Venting from Pressurized Reservoir into the Atmosphere

A critical assessment of factors affecting the flammability of R-1234yf in a frontal collision