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Labeling of retina and optic tectum phospholipids in chickens exposed to light or dark.

The labeling of retina ganglion cell and optic tectum phospholipids was determined in chickens given an intraocular injection of 32P and then either exposed to light or maintained in the dark. Significantly higher labeling was found in the optic tectum phospholipids of light-exposed compared with dark-maintained animals after 3-24 h of labeling. In the ganglion cells, the labeling of phospholipids increased in dark with respect to light at 15 and 30 min of labeling; from 60 min to 24 h, the labeling of phospholipids was significantly higher in light with respect to dark, even if the precursor pool showed a higher labeling in dark at all times studied. When labeling was allowed to proceed in the dark for 30 min and then half of the animals were exposed to light for 15 min, the labeling of ganglion cell phospholipids of light-exposed animals was significantly higher than those of animals kept in the dark. No individual phospholipid accounted for the differences observed in the labeling of the total phospholipid pool. These results are interpreted as an increase in the biosynthesis of phospholipids in the ganglion cell somas in light with respect to dark.

Adaptation, Ocular↗

The role of microsomal phospholipids and their fatty acid composition in the control of hepatic metabolism of lignocaine.

1. Sex differences exist in the metabolism of lignocaine by the rat liver. Microsomal phospholipids have been implicated in the control of these sex differences. Induction of diabetes in the male rat abolishes these sex differences. The difference in drug metabolism between the male and female rat is, thus, the same as that between the control and diabetic male rat. 2. By using reconstitution of delipidated male microsomal proteins with male-, female- and diabetic-derived phospholipids as well as synthetic phospholipids, it should be possible to delineate the role of phospholipids in the control of drug metabolism. 3. Female- and diabetes-derived phospholipids decrease the activity of the male-specific lignocaine N-deethylase specifically by between 35 and 52%. 4. Analysis of the phospholipid classes and fatty acid content of the various fractions indicated that stearic acid content was increased and arachidonic acid content decreased in both female- and diabetic-derived lipids as compared to control males. Linoleic acid content was decreased in female- but increased in diabetic-derived lipids as compared to control males. Subsequent correlation to N-deethylase activity, however, rules out all but the arachidonic acid content of the phospholipids as a controlling factor of lignocaine metabolism. 5. Use of synthetic phosphatidylcholine (PC) species for reconstitution indicates that diarachidonyl-PC is the most efficient at activating the N-deethylase and indicates that the degree of unsaturation of the fatty acyl side-chains of PC is of major importance in the regulation of this enzyme activity. 6. The presence of unsaturated fatty acids, and especially arachidonic acid, in the phospholipids is, thus, a major controlling influence on the specific activation of lignocaine N-deethylase in the rat liver.

Animals↗

Incorporation of 15-hydroxyeicosatrienoic acid in specific phospholipids of cultured human keratinocytes and psoriatic plaques.

15-hydroxyeicosatrienoic acid, 15-HETrE, the 15-lipoxygenase product of dihomogammalinolenic acid (DGLA), can inhibit the biosynthesis of the proinflammatory eicosanoids leukotriene B4 (LTB4) and 12-hydroxyeicosatetraenoic acid (12-HETE). The purpose of the present study was to investigate the incorporation of [14C]15-HETrE in specific membrane phospholipids of cultured human keratinocytes in vitro. [14C]15-HETrE was rapidly incorporated into keratinocytes. When a plateau was reached after 3 hours, 15% of the added radioactivity was incorporated into lipids; 96.5% into phospholipids (PL) and 3.5% into neutral lipids (NL). Within the phospholipid classes, [14C]15-HETrE showed selectivity for incorporation into phosphatidylinositol (PI). The mean proportion of [14C]15-HETrE in the PI, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was 83.2%, 8.5% and 8.3%, respectively. We then investigated the incorporation of 15-HETrE in epidermal phospholipids of psoriatic skin intralesionally injected with 15-HETrE. Four patients took part in the study. In each patient four identical plaques were injected with 0.65 ml of 2.0 microM, 6.2 microM, 18.6 microM of 15-HETrE (0.4 micrograms, 1, 2 micrograms and 3.6 micrograms respectively) or 0.65 ml of 0.88% NaCl twice a week. After 3 wk keratome biopsies were obtained from the treated plaques. Phospholipids extracted from the skin biopsies were separated into major classes by two-dimensional thin layer chromatography. 15-HETrE was then released from specific phospholipids after treatment with phospholipase A2 and identified by reverse phase and straight phase high performance liquid chromatography. There was a dose-dependent incorporation of 15-HETrE into the specific phospholipids PI and PC. When expressed as ng 15-HETrE/micrograms phospholipid phosphate, 15-HETrE accumulated preferentially in PI.(ABSTRACT TRUNCATED AT 250 WORDS)

8,11,14-Eicosatrienoic Acid↗

Phospholipid synthesis by Staphylococcus aureus during (Sub)Lethal attack by mammalian 14-kilodalton group IIA phospholipase A2.

Killing of gram-positive bacteria by mammalian group IIA phospholipases A2 (PLA2) requires the catalytic activity of the enzyme. However, nearly complete degradation of the phospholipids can occur with little effect on bacterial viability, suggesting that PLA2-treated bacteria can biosynthetically replace phospholipids that are lost due to PLA2 action. In the presence of albumin, phospholipid degradation products are quantitatively sequestered extracellularly. In the absence of albumin, the bacteria retain and substantially reutilize the phospholipid breakdown products and survive an otherwise lethal dose of PLA2. PLA2-treated bacteria also continue to incorporate sodium [2-(14)C]acetate into phospholipids, suggesting that the bacteria are attempting to repair the damaged membranes by de novo synthesis of phospholipids. To determine whether PLA2 action also triggers activation of bacterial lipolytic enzymes, the effects of nisin and PLA2 on the degradation of S. aureus lipids were compared. In contrast to nisin treatment, PLA2 treatment does not stimulate endogenous phospholipase activity in S. aureus. These findings show that S. aureus responds to PLA2 attack by continued phospholipid (re)synthesis by both de novo and salvage pathways. The fate of PLA2-treated S. aureus therefore appears to depend on the relative rates of phospholipid degradation and synthesis.

Acetates↗

Differential membrane phospholipid synthesis during the cell cycle of Caulobacter crescentus.

The pattern of phospholipid synthesis during the cell cycle of Caulobacter crescentus has been determined. Although the phospholipid composition of swarmer and stalked cells was indistinguishable in continuously labeled cultures if the two cell types were pulse-labeled for a short time period, marked differences in the pattern of phospholipid synthesis were detected. Pulse-labeled swarmer cells exhibited a higher proportion of phosphatidic acid and a lower proportion of phosphatidylglycerol. In addition, minor phospholipids were detected in the swarmer cells that were not detected in stalked cells. Stalked cells that developed directly from swarmer cells showed that same phospholipid profile as the swarmer cells. The switch to the second phospholipid profile was observed to occur at the predivisional cell stage. Because cell division then yielded a swarmer cell with a different phospholipid profile than its sibling stalked cell, the cell division process may trigger a mechanism which alters the pattern of phospholipid synthesis.

Bacteria↗

Rhodopseudomonas sphaeroides membranes: alterations in phospholipid composition in aerobically and phototrophically grown cells.

The effects of growth conditions on phospholipid composition in Rhodopseudomonas sphaeroides have been reexamined. The levels of phosphatidylethanolamine (27 to 28%), phosphatidylglycerol (23 to 24%), and phosphatidylcholine (11 to 18%) were very similar in cells grown aerobically or phototrophically at a high light intensity, consistent with findings for another member of Rhodospirillaceae. In addition, an unknown phospholipid species was detected which comprised 20 to 30% of the total phospholipid in these cells. In cells growing phototrophically at low-intensity illumination, the level of phosphatidylethanolamine increased by about 1.6-fold and that of the unknown phospholipid markedly decreased. Although the synthesis of photosynthetic pigments, light-harvesting protein, and intracytoplasmic photosynthetic membranes also increased markedly, the ratios of individual phospholipid species were essentially identical in photosynthetic membrane and cell wall fractions purified from these cells. Since a significant exchange of lipids apparently did not occur during the isolation of these fractions, it was suggested that the changes in cellular phospholipid accumulation were not due to a unique composition within the photosynthetic membrane. Instead, these phosphoglyceride changes were found to be related to overall phospholipid metabolism and could be accounted for principally by differences in biosynthetic rates. These results, together with studies in nutrient-restricted aerobic cells, suggested that the mechanism by which phospholipid levels are regulated may be related to radiant energy flux rather than cellular energy limitation.

Aerobiosis↗

Alterations in the phospholipid composition of Rhodopseudomonas sphaeroides and other bacteria induced by Tris.

Alterations in the phospholipid head group composition of most strains of Rhodopseudomonas sphaeroides, as well as Rhodopseudomonas capsulata and Paracoccus denitrificans, occurred when cells were grown in medium supplemented with Tris. Growth of R. sphaeroides M29-5 in Tris-supplemented medium resulted in the accumulation of N-acylphosphatidylserine (NAPS) to as much as 40% of the total whole-cell phospholipid, whereas NAPS represented approximately 28 an 33% of the total phospholipid when R. capsulata and P. denitrificans respectively, were grown in medium containing 20 mM Tris. The accumulation of NAPS occurred primarily at the expense of phosphatidylethanolamine in both whole cells and isolated membranes of R. sphaeroides and had no detectable effect on cell growth under either chemoheterotrophic or photoheterotrophic conditions. Yeast extract (0.1%) and Casamino Acids (1.0%) were found to be antagonistic to the Tris-induced (20 mM) alteration in the phospholipid composition of R. sphaeroides. The wild-type strains R. sphaeroides 2.4.1 and RS2 showed no alteration in their phospholipid composition when they were grown in medium supplemented with Tris. In all strains of Rhodospirillaceae tested, as well as in P. denitrificans, NAPS represented between 1.0 and 2.0% of the total phospholipid when cells were grown in the absence of Tris. [32P]orthophosphoric acid entered NAPS rapidly in strains of R. sphaeroides that do (strain M29-5) and do not (strain 2.4.1) accumulate this phospholipid in response to Tris. Our data indicate that the phospholipid head group composition of many Rhodospirillaceae strains, as well as P. denitrificans, is easily manipulated; thus, these bacteria may provide good model systems for studying the effects of these modifications on membrane structure and function in a relatively unperturbed physiological system.

Membrane Lipids↗

Light-mediated regulation of phospholipid synthesis in Rhodopseudomonas sphaeroides.

The relationship between the culture levels of guanosine-5'-diphosphate-3'-diphosphate (ppGpp) and the rates of synthesis and accumulation of cellular phospholipids was examined in cultures of Rhodopseudomonas sphaeroides that had been subjected to immediate decreases in incident light intensity. After a high-to-low light transition of high-light-adapted cells, an immediate inhibition of total cellular phospholipid production occurred coincident with a rapid accumulation of culture ppGpp. The inhibition of phospholipid accumulation occurred at the level of phospholipid synthesis rather than turnover, and both the extent of ppGpp accumulation and the degree of inhibition of phospholipid synthesis were directly dependent upon the magnitude of the light transition. Maximum inhibition (greater than 90%) of the rate of cellular phospholipid synthesis occurred after transitions from 5,350 to 268 1x and lower, including transitions to the dark, with comparable inhibition being exerted upon the rates of synthesis of individual species of phospholipids. Reinitiation of culture phospholipid accumulation in cultures shifted from 5,350 to 1,070 1x and lower occurred 65 to 70 min subsequent to the downshift in light intensity, apparently irrespective of the culture level of ppGpp.

Guanosine Tetraphosphate↗

Regulation of phospholipid synthesis in phosphatidylserine synthase-deficient (chol) mutants of Saccharomyces cerevisiae.

chol mutants of Saccharomyces cerevisiae are deficient in the synthesis of the phospholipid phosphatidylserine owing to lowered activity of the membrane-associated enzyme phosphatidylserine synthase. chol mutants are auxotrophic for ethanolamine or choline and, in the absence of these supplements, cannot synthesize phosphatidylethanolamine or phosphatidylcholine (PC). We exploited these characteristics of the chol mutants to examine the regulation of phospholipid metabolism in S. cerevisiae. Macromolecular synthesis and phospholipid metabolism were examined in chol cells starved for ethanolamine. As expected, when chol mutants were starved for ethanolamine, the rates of synthesis of the phospholipids phosphatidylethanolamine and PC declined rapidly. Surprisingly, however, coupled to the decline in PC biosynthesis was a simultaneous decrease in the overall rate of phospholipid synthesis. In particular, the rate of synthesis of phosphatidylinositol decreased in parallel with the decline in PC biosynthesis. The results obtained suggest that the slowing of PC biosynthesis in ethanolamine-starved chol cells leads to a coordinated decrease in the synthesis of all phospholipids. However, under conditions of ethanolamine deprivation in chol cells, the cytoplasmic enzyme inositol-1-phosphate synthase could not be repressed by exogenous inositol, and the endogenous synthesis of the phospholipid precursor inositol appeared to be elevated. The implications of these findings with respect to the coordinated regulation of phospholipid synthesis are discussed.

CDPdiacylglycerol-Serine O-Phosphatidyltransferase↗

Lung surfactant in a cystic fibrosis animal model: increased alveolar phospholipid pool size without altered composition and surface tension function in cftrm1HGU/m1HGU mice.

BACKGROUND: Progressive pulmonary dysfunction is a characteristic symptom of cystic fibrosis (CF) and is associated with functional impairment and biochemical alterations of surfactant phospholipids in the airways. However, the fundamental question of whether surfactant alterations in the CF lung are secondary to the pulmonary damage or are present before initiation of chronic infection and inflammation has yet to be resolved in patients with cystic fibrosis but can now be addressed in CF mice that exhibit the basic defect in the airways. A study was therefore undertaken to investigate the pool sizes, composition, and function of lung surfactant in the non-infected cftrm1HGU/m1HGU mouse. METHODS: The amount and composition of phospholipid classes and phosphatidylcholine molecular species were determined in bronchoalveolar lavage (BAL) fluid and lavaged lungs by high performance liquid chromatography (HPLC). Surfactant protein A (SP-A) levels in BAL fluid were determined by ELISA and surfactant for functional measurements was isolated from BAL fluid by differential ultracentrifugation. Equilibrium and minimal surface tension of surfactant was assessed by the pulsating bubble surfactometer technique. MF1, BALB/c, C57/BL6, and C3H/He mice served as controls. RESULTS: BAL fluid of cftrm1HGU/m1HGU mice contained 1.02 (95% confidence interval (CI) 0.89 to 1.16) mumol phospholipid and 259 (239 to 279) ng SP-A. BAL fluid of MF1, BALB/c, C57BL/6, and C3H/He mice contained 0.69 (0.63 to 0.75), 0.50 (0.42 to 0.57), 0.52 (0.40 to 0.64), and 0.45 (0.27 to 0.63) mumol phospholipid, respectively. After correction for the different body weights of mouse strains, phospholipid levels in BAL fluid of cftrm1HGU/m1HGU mice were increased by 64 (52 to 76)%, 60 (39 to 89)%, 72 (45 to 113)%, and 92 (49 to 163)%, respectively, compared with controls. The amount of SP-A in BAL fluid and the composition of phospholipid as well as phosphatidylcholine molecular species in BAL fluid and lung tissue was unchanged in cftrm1HGU/m1HGU mice compared with controls. The increase in phospholipids in BAL fluid of cftrm1HGU/m1HGU mice resulted from an increased fraction of large aggregates which exhibited normal surface tension function. CONCLUSION: In cftrm1HGU/m1HGU mice surfactant homeostasis is perturbed by an increased phospholipid pool in the alveolar compartment.

Analysis of Variance↗

Cell biology of cardiac mitochondrial phospholipids.

Phospholipids are important structural and functional components of all biological membranes and define the compartmentation of organelles. Mitochondrial phospholipids comprise a significant proportion of the entire phospholipid content of most eukaroytic cells. In the heart, a tissue rich in mitochondria, the mitochondrial phospholipids provide for diverse roles in the regulation of various mitochondrial processes including apoptosis, electron transport, and mitochondrial lipid and protein import. It is well documented that alteration in the content and fatty acid composition of phospholipids within the heart is linked to alterations in myocardial electrical activity. In addition, reduction in the specific mitochondrial phospholipid cardiolipin is an underlying biochemical cause of Barth Syndrome, a rare and often fatal X-linked genetic disease that is associated with cardiomyopathy. Thus, maintenance of both the content and molecular composition of phospholipids synthesized within the mitochondria is essential for normal cardiac function. This review will focus on the function and regulation of the biosynthesis and resynthesis of mitochondrial phospholipids in the mammalian heart.

Animals↗

In vitro effect of free bile acids on the bile canalicular membrane phospholipids in the rat.

Liver cell plasma membranes of male rats were isolated and separated into two fractions, one rich in bile canalicular membranes (BCM) and the other comprising the rest of the plasma membrane (PM). Aliquots of BCM, PM, and microsomes were incubated with deoxycholic, chenodeoxycholic, or cholic acid at bile acid - membrane phospholipid mole ratios up to 100, and the phospholipid solubilization from the PM and from microsomes was linear and apparently nonselective, while that from BCM was biphasic and distinctly selective. Phosphatidyl choline and phosphatidyl ethanolamine made up 90% of the phospholipids solubilized from the BCM at a bile acid - membrane phospholipid mole ratio sufficient to solubilize about 50% of the total phospholipids of the BCM. Of particular interest was the observation that the molecular species and fatty acid composition of the phospholipids solubilized from the BCM under these experimental conditions were similar to those of bile obtained from the same animal, and were quite unlike those solubilized at higher bile acid - phospholipids mole ratios. The data are discussed in terms of the mechanism of the biliary secretion of phospholipids.

Animals↗

Expansion of phospholipid pool size of rat intestinal villus cells during fat absorption.

The effect of fat absorption upon the phospholipid pool size of the intestinal mucosal cells was determined in rats receiving fatty emulsions as a bolus by stomach tube or as multiple meals in the form of fat-laden laboratory chow. The phospholipid content of the mucosal scrapings and of the isolated villus cells was determined 3 to 34 h after the meals and was compared with the phospholipid content of cells from similar animals receiving water alone or 10% sucrose in water. It was shown that continuously fed animals averaged 5-10% and single meal fed animals up to 40% higher phospholipid content in their mucosal cells than the corresponding controls, when compared per milligram cell protein. The expansion of the phospholipid pool involved all phospholipid classes and correlated well with the phospholipid composition of prechylomicrons and of microsomal membranes, which undergo a significant proliferation during fat absorption. The apparent lower expansion of the phospholipid pool in the continuously fed animals correlated with the lower triacylglycerol content of the lumen and of the cells at these times.

Animals↗

Further evidence for enhanced phospholipid synthesis by rat jejunal villus cells during fat absorption.

The effect of fat absorption on the phospholipid turnover of rat intestinal mucosa was determined in animals receiving single fatty meals by stomach tube or multiple meals in the form of corn-oil-soaked laboratory chow diet. The specific activity and relative specific activity of the total phospholipids and of individual phospholipid classes were measured in the isolated jejunal villus cells of fasting and fat-fed animals following an injection of radioactive inorganic phosphate 0.5-31 h prior to sacrifice, which was scheduled to coincide with the peak of fat absorption (2.5-3 h after the last meal). It was shown that the relative specific activity of the fat-absorbing cells increased by about 33% when the samples were taken 0.5 h after intravenous injection of radioactive phosphate. Samples taken 11 and 31 h after the introduction of the radioactive phosphate showed about 16% decrease in the relative specific activity of the phospholipids of the fat-absorbing cells when compared with the fasting controls. These changes in the relative specific activity of the total phospholipids included all phospholipid classes and corresponded to the recently described expansion of the cellular phospholipid pool owing partly to increased de novo synthesis of the membrane phospholipids. The present results are consistent with the known biochemical and physiological changes taking place in the mucosal cells during fat absorption and transport and find support in various less direct biochemical and morphometric measurements.

Animals↗

Effect of gentamicin on phospholipid metabolism in cultured rabbit proximal tubular cells.

We examined the hypothesis that the accumulation of phospholipid in cells exposed to gentamicin is due to impaired degradation. Experiments were performed in rabbit proximal tubular cells grown in primary culture. Cells exposed to 10(-3) M gentamicin manifested myeloid body formation and a progressive increase in total phospholipid that by day 6 was 44% higher than that of control cells and reflected increases of phosphatidylinositol of 235%, phosphatidylcholine of 60%, phosphatidylethanolamine of 90%, and phosphatidylserine of 55% above control values. Gentamicin impaired the degradation of these phospholipids. The t1/2 of the phospholipid pool labeled with [3H]myoinositol increased 146% from 1.17 (control) to 2.88 days (gentamicin); the t1/2 of the [3H]choline pool increased 34% from 1.77 to 2.38 days; the t1/2 of the [3H]ethanolamine pool increased 57% from 3.14 to 4.93 days; the t1/2 of the [3H] serine pool increased 37% from 6.30 to 8.63 days. Exposure of cells to gentamicin for 2 days also stimulated increased incorporation of [3H]myoinositol (68%) and [3H]ethanolamine (59%) into phospholipid. The data are consistent with the hypothesis that gentamicin inhibits the activity of lysosomal phospholipases that results in the accumulation of phospholipid within the lysosome in the form of myeloid bodies. Increased phospholipid synthesis may represent a compensatory response to the impaired lysosomal degradation of phospholipid. We postulate that the preferential increase of phosphatidylinositol reflects the capacity of the polycationic gentamicin to interact electrostatically with the anionic phosphoinositides and inhibit their turnover.

Animals↗

Phospholipid peroxidation deacylation and remodeling in postischemic skeletal muscle.

Reperfusion of ischemic skeletal muscle is associated with white blood cell (WBC) sequestration and hydroperoxy-conjugated diene (HCF) formation, a marker of free radical-mediated phospholipid peroxidation. The purpose of this study was to define the kinetics of phospholipid fatty acyl peroxidation, deacylation, and remodeling in postischemic skeletal muscle during prolonged reperfusion in vivo, and to determine whether reperfusion with WBC and plasma-depleted blood would attenuate postischemic phospholipid peroxidation and myocyte necrosis. The isolated, paired, canine gracilis muscle model was used. After 5 h of ischemia, muscles underwent unaltered reperfusion or initial reperfusion with WBC-deficient blood cells resuspended in hydroxyethyl starch, followed by return to normal circulation (modified reperfusion). The concentration of native fatty acids and HCDs of linoleic acid extracted from muscle phospholipids was quantified by gas chromatography and positively identified by mass spectrometry. Ischemia and reperfusion resulted in phospholipid deacylation and a selective increase in phospholipid stearic acid content, but had no effect on total phospholipid phosphorus. Modified reperfusion decreased 1) early HCD formation (54%) and 2) postischemic skeletal muscle necrosis (49%). These data suggest that reperfusion results in phospholipid deacylation and remodeling, and that the initial oxidant stress during reperfusion may be a significant determinant of ultimate muscle necrosis.

Acylation↗

Alterations in renal cortical phospholipid content induced by gentamicin: time course, specificity, and subcellular localization.

Increasing evidence suggests that membrane phospholipids are a major site of interaction between gentamicin and renal tubular cells. To help assess the impact of this interaction on renal tubular cell phospholipid metabolism, renal cortical phospholipid levels were assessed serially during treatment with nephrotoxic doses of gentamicin in the rat. Within 15 h of treatment with a single 100 mg/kg dose of gentamicin, significant increases in phosphatidylinositol and phosphatidic acid occurred, and further increases in these acidic phospholipids were seen 24 h after two and four daily doses. No consistent sustained changes were observed in total phospholipid levels or in levels of other phospholipids. None of these gentamicin treatment regimens was associated with wide-spread tubular cell necrosis in the rat at the intervals studied. In contrast, during models of acute renal failure secondary to HgCl2 and glycerol, increases in phosphatidylinositol and phosphatidic acid were found only after the development of wide-spread tubular cell necrosis. Subcellular fractionation studies showed that the increase in phosphatidylinositol produced by gentamicin involved multiple cell membranes, including mitochondria, brush border membranes, endoplasmic reticulum, and lysosomes, suggesting that the effects of gentamicin on renal cortical acidic phospholipid metabolism are not limited to inhibition of intralysosomal degradative processes but, rather, occur in such fashion as to influence the phospholipid composition of multiple subcellular membranes.

Animals↗

Lipoprotein-like phospholipid particles inhibit the smooth muscle cell cytotoxicity of lysophosphatidylcholine and platelet-activating factor.

Oxidation of LDL is associated with degradation of phosphatidylcholine into platelet-activating factor (PAF)-like phospholipids and lysophosphatidylcholine (LPC). Exposure of cultured human smooth muscle cells to PAF and LPC in a concentration of 25 micromol/L was found to result in complete cell death, as assessed by the MTT cytotoxicity assay and cell counting. Addition of 50 microg/mL apolipoprotein A-I- and apolipoprotein A-I(Milano)-containing phospholipid particles completely inhibited this cytotoxicity. Phospholipid complexes alone were almost as effective, whereas free apolipoprotein A-I(Milano) and albumin were without effect, suggesting that the effect was phospholipid dependent. Experiments using [14C]LPC demonstrated that apolipoprotein A-I- and apolipoprotein A-I(Milano)-containing phospholipid particles effectively bind LPC. The results show that HDL-like phospholipid particles effectively inhibit the toxic effect of phospholipids and other lipid-soluble factors. The ability of HDL to inhibit the proinflammatory and toxic effects of phospholipids generated during oxidation of LDL may be responsible for part of the antiatherogenic properties of HDL.

Apolipoprotein A-I↗