Contrasting effects of alloantiserum and xenoantiserum on cell-mediated lysis of tumor cells

The effect of anti-EL-4 serum on antibody-dependent cytotoxicity (ADCC) and cell-mediated cytotoxicity (CMC) was studied in allogeneic and xenogeneic systems. Inbred strains of BALB/c mice and Lewis rats were immunized with EL-4 tumor cells. Using microcytotoxic assays of ⁵¹Cr release from labeled EL-4 cells, complement-dependent cytolysis, ADCC, and CMC were determined. Complement-dependent cytolysis was observed in both systems. Although ADCC was demonstrated in both systems, the kinetics of cytolysis were different. Xenoantisera and alloantisera had opposite effects on CMC. Incubation of EL-4 target cells with BALB/c anti-EL-4 serum resulted in inhibition of CMC by immune BALB/c spleen cells. In contrast, treatment of EL-4 target cells with Lewis anti-EL-4 serum potentiated the CMC of immune Lewis spleen cells. It is thought that differences in the strength of response, antibody characteristics, and effector cells may determine the degree of inhibition or potentiation observed in these systems.     

Alteration of the fatty acid composition of membrane phospholipids in mouse lymphoid cells

A simple method is described for introducing exogenous fatty acids into the membrane phospholipids of the murine leukemia cell EL-4, and into the membrane phospholipids of resting mouse lymphocytes. The method involves culturing of the cells with free or methylated fatty acids at concentrations up to 50 microgram/ml. The presence of serum in the culture medium does not interfere with fatty acid uptake, but does increase the growth rate and viability of the cells. Membrane lipid composition returns to normal after the cells are grown in medium without exogenous fatty acid. Fractionation of the cell membranes confirmed that exogenous fatty acids were incorporated into the phospholipids of the plasma membrane.     

Cis-unsaturated fatty acids induce both lipogenesis and calcium binding in adipocytes

The addition of 0.4-3 mM of cis-unsaturated fatty acids such as oleic acid (18:1) or linoleic acid (18:2) to intact rat adipocytes stimulated lipogenesis at 37 degrees C. Saturated or trans-unsaturated fatty acids were ineffective. Fluorescence photobleaching recovery studies performed under similar conditions indicated that the cis-unsaturated fatty acids do not alter lateral mobility of either a lipid probe or a general protein marker in the plasma membrane. A high concentration (7 mM) of Ca2+, which by itself has some stimulatory effect on lipogenesis, significantly potentiated the effect of oleic acid on this insulin-like activity. Measurement of 45Ca2+ binding by fat cells has indicated that cis-unsaturated (but not saturated) fatty acids increased 12- to 20-fold the amount of Ca2+ associated with the cells. The dependence of this effect on the fatty acid concentration correlates well with the effect of the fatty acid on the induction of lipogenesis. Our results suggest that cis-unsaturated fatty acids affect membrane organization in a manner which induces a significant increase in membrane associated or intracellular Ca2+. This increase may be responsible for inducing exocytotic-like processes which facilitate translocation of glucose transport activity from storage sites to the plasma membrane and thus produce an insulin-like effect.     

Radiation studies of Acholeplasma laidlawii: the role of membrane composition

Acholeplasma laidlawii, a mycoplasma, is unable to synthesize unsaturated fatty acids but it will incorporate them into its plasma membrane if they are supplied exogeneously. Thus the fatty acid composition of the cell membrane can be defined by growing the organism in media containing specific fatty acids. We obtained cells with predominantly one type of unsaturated fatty acid (either oleic, linoleic or linolenic acid) or cells with only saturated fatty acid in the cell membrane. The cells were irradiated with 7 MeV electrons and the effect of membrane fatty acid composition on cell survival was examined. At 200 Gy/min and 0.5 degrees C (melting ice) there was little difference in the radiation sensitivities of the cells grown in unsaturated fatty acids either in aerated or anoxic radiation conditions. However, the cells containing saturated fatty acids irradiated in anoxic conditions were markedly more sensitive than the cells containing unsaturated fatty acids. At 200 Gy/min and 37 degrees C the two types of cells were of similar sensitivity both in aerated and anoxic radiation conditions. At 5 Gy/min at 0.5 degrees C the cells containing linolenic acid (18:3) were less sensitive than those containing solely saturated fatty acids. However, at 5 Gy/min at 37 degrees C there was no difference in sensitivity between these two types of cell. Our results strongly argue against the involvement of lipid peroxidation as a molecular change leading to cell death.     

Modulation of cell-mediated cytotoxicity function after alteration of fatty acid composition in vitro

Fatty acids incorporated into cytotoxic T lymphocytes (CTL) during in vitro stimulation can enhance or inhibit the subsequent expression of cell-mediated cytotoxicity, depending on the class of fatty acid. Unsaturated fatty acids enhance cytolysis, whereas saturated fatty acids inhibit it. The effects of fatty acids on cytolysis can be mediated in the absence of cell division, thus eliminating relative clonal amplification or contraction as a basis for the observed effects. Nevertheless, the net result of fatty acid alteration is an increase (unsaturated fatty acids) or decrease (saturated fatty acids) in the frequency, in the treated immune population, of CTL capable of lysing target cells. These observations are best explained by a model in which fatty acid incorporated into cell membrane phospholipids results in a direct recruitment into or out of the pool of CTL within the immune population capable of lysing target cells under the conditions employed to assay cytotoxicity.     

Uptake of l-Glutamate and Taurine in Neuroblastoma Cells with Altered Fatty Acid Composition of Membrane Phospholipids

Abstract: Effects of altered composition of membrane lipids on high-affinity uptake of l -glutamate and taurine were studied in an established neuroblastoma cell line M₁. Increase in participation of certain fatty acids (20: 5ω3 and 22: 5ω3) as constituents of membrane lipids resulted in a fourfold increase in the maximum initial rate of l -glutamate uptake (V_max) while increase in V_max of taurine uptake was much smaller. Neither structural requirements of l -glutamate uptake nor passive permeability of the membrane to l -glutamate or taurine seemed to be influenced by the alterations in the lipid composition. Since increased proportions of 20: 5ω3 and 22: 5ω3 in the membrane phosphatides caused no dramatic changes in kinetic parameters of taurine uptake and incorporation of either linoleic or linolenic acid alone into the phosphatides had only a relatively small effect on some of the measured parameters, the possibility of a specific relationship between 22: 5ω3 and/or 20: 5ω3 and l -glutamate uptake is discussed. Unlike l -glutamate uptake systems in other preparations, the high-affinity uptake system of l -glutamate in neuroblastoma cells did not readily accept l -aspartate as a substrate.     

Spin labelling studies of cytolysis induced by fatty acids

Rat thymocytes, spleen lymphocytes and isolated nuclei were incubated with fatty acids and then labelled with 5-doxylstearic acid and 12-doxylstearic acid. The ESR spectra only in the case of 5-doxylstearic acid showed changes which were demonstrable only under those conditions which resulted in cytolysis. Thymocytes in medium with 10% serum showed the effect at 10 microM, splenic lymphocytes at 100 microM. The effect was maximal at 2 min and was not enhanced by higher concentrations. The uptake of fatty acid by spleen cells required to cause this change was determined using 14C-oleic acid, to be 0.6 mumol/g tissue. This quantity is less than that required (label:lipid ratio less than 1:10) to produce major perturbations in membranes. Free fatty acids of C-8 to C-18 produced the effect, but not esters or amides. It was concluded that free fatty acids induce changes proximal to the polar region of membrane lipids which, if not progressive and essential to the ultimate process of lysis, are at least indicative of impending cell death at an early time.     

Phospholipid composition of Rickettsia prowazeki grown in chicken embryo yolk sacs.

The phospholipid composition and phospholipid fatty acid composition of purified Rickettsia prowazeki were determined. The lipid phosphorous content was 6.8 +/- 1.3 microgram/mg of total rickettsial protein. The major phospholipid was phosphatidylethanolamine (60 to 70%); phosphatidylglycerol constituted 20%, and phosphatidylcholine constituted 15%. Small amounts of phosphatidylserine and cardiolipin were detected. The principal fatty acids were 18:1, 16:1, and 16:0. The fatty acid composition of the phosphatidylcholine in the rickettsial extracts was very different than that of the other rickettsial phosphatides and very similar to that of normal yolk sac phosphatidylcholine. The specific of the phosphatidylcholine of rickettsiae grown in the presence of 32P was markedly lower than that of phosphatidylethanolamine and phosphatidylglycerol. It is suggested that the phosphatidylcholine in the rickettsial extract is yolk sac derived and either tightly absorbed or exchanged into the rickettsial membrane.     

Human erythrocyte membrane fluidity and insulin binding are independent of dietary trans fatty acids

Substitution of selected saturated fatty acids of the diet of 29 men and 29 women with cis or trans monounsaturated fatty acids did not affect erythrocyte membrane fluidity, insulin binding, and the membrane cholesterol and phospholipid concentrations. Subjects were fed four different controlled diets with a total fatty acid content of 39 to 40 energy percent for four 6-week periods in a Latin square design. The diets were: (1) high oleic acid (16.7 energy percent oleic); (2) moderate trans (3.8 energy percent trans fatty acids); (3) high trans (6.6 energy percent trans fatty acids); and saturated (16.2 energy percent lauric + myristic + palmitic acids). There were no significant diet effects on red cell ghost fluidity determined by fluorescence polarization of the hydrocarbon probe 1,6-diphenyl-1,3,5-hexatriene (DPH) and the polar analog trimethylammonium-DPH (TMA-DPH). There were limited diet effects on fluidity of membranes as determined with DPH-propionic acid (DPH-PA) for the men. Insulin binding was more closely associated with anisotropy of fluorescence of the surface probe, DPH-PA, than with that of the other probes, which is compatible with the localization of the insulin receptor in a domain at the cell membrane surface.     

Temperature adaptation of biological membranes. Compensation of the molar activity of cytochrome c oxidase in the mitochondrial energy-transducing membrane during thermal acclimation of the carp (cyprinus carpio L.)

The phospholipid composition, fatty acid pattern and cholesterol content are studied in mitochondria of red lateral muscle of carp acclimated to high and low environmental temperatures.The results of the experiments are: mitochondria from cold-acclimated carp contain higher proportions of ethanolamine phosphatides than mitochondria from warm-acclimated fish, the opposite is true for the choline phosphatides. Thus, at constant pH, the membrane phospholipids are slightly more negatively charged at low acclimation temperature. The total plasmalogen content is reduced in the cold; this reduction is caused by a decrease in the proportion of the choline plasmalogens. The ethanolamine phosphoglycerides contain approx. 20% of the alk-1-enyl acyl type, irrespective of the acclimation temperature. There is no temperature-dependent difference in the low proportion of cholesterol.The fatty acids of total mitochondrial phospholipids are characterized by large amounts of the n-3 and n-6 families. The ratio of unsaturated to saturated fatty acids and the unsaturation index are remarkably higher than those reported for comparable mammalian phospholipids. Cold acclimation of carp does not significantly increase the unsaturation of total phospholipids. A fatty acid analysis of the main isolated phospholipids, however, shows that cold acclimation considerably increases unsaturation of the neutral phosphatidylcholine, whereas it dramatically decreases unsaturation of the negatively charged cardiolipin. It is suggested that the observed fatty acid substitution in phosphatidylcholine indicates a temperature-induced fluidity adaptation within the mitochondrial lipid bilayer, whereas the inverse acclimation pattern of cardiolipin provides a suitable lipid to accommodate the temperature-dependent modifications in the dynamic surface shape of integral membrane proteins.     

Differential effects of temperature and exogenous fatty acids on mitogen-induced proliferation in channel catfish T and B lymphocytes

1. Exogenously supplied, BSA complexed saturated and unsaturated fatty acids were compared for their effects on mitogen-induced DNA synthesis in channel catfish T and B lymphocytes. 2. At "permissive" in vitro temperatures (27 degrees C), high concentrations (greater than or equal to 240 microM) of all the fatty acids used were inhibitory. However, at lower concentrations (80-160 microM), differences were noted in the ability of some fatty acids to modulate mitogen responses. While palmitic acid (16:0) and linoleic acid (18:2) had little effect on LPS-induced B cell- or Con A-induced T cell proliferation, stearic acid (18:0) suppressed while oleic acid (18:1) enhanced T cell responses only. 3. Adding equimolar amounts of 18:0 and 18:1 obviated the effects of singularly added fatty acids on T cell mitogenesis. 4. 18:1 was used to successfully "rescue" approximately 60% of the Con A-induced T cell proliferation normally inhibited at "nonpermissive" in vitro temperatures (17 degrees C). 5. While B cells readily appear to desaturate 18:0 and synthesize unsaturated fatty acids, T cells accumulate comparatively large amounts of 18:0 in membrane associated phospholipids. 6. It is proposed that 18:1 enhances T cell responses at permissive high temperatures and rescues suppressed T cell responses at nonpermissive low temperatures by increasing membrane fluidity.     

Endothelial cell fatty acid unsaturation mediates cold-induced oxidative stress

Ultraprofound hypothermia (< 5 degrees C) induces changes to cell membranes such as liquid-to-gel lipid transitions and oxidative stress that have a negative effect on membrane function and cell survival. We hypothesized that fatty acid substitution of endothelial cell lipids and alterations in their unsaturation would modify cell survival at 0 degrees C, a temperature commonly used during storage and transportation of isolated cells or tissues and organs used in transplantation. Confluent bovine aortic endothelial cells were treated with 18-carbon fatty acids (C18:0, C18:1n-9, C18:2n-6, or C18:3n-3), C20:5n-3 or C22:6n-3 (DHA), and then stored at 0 degrees C without fatty acid supplements. Storage of control cells caused the release of lactate dehydrogenase (LDH) and a threefold increase in lipid peroxidation (LPO) when compared to control cells not exposed to cold. Pre-treating cells with C18:0 decreased the unsaturation of cell lipids and reduced LDH release at 0 degrees C by 50%, but all mono- or poly-unsaturated fatty acids increased injury in a concentration-dependent manner and as the extent of fatty acid unsaturation increased. DHA-treatment increased cell fatty acid unsaturation and caused maximal injury at 0 degrees C, which was prevented by lipophilic antioxidants BHT or vitamin E, the iron chelator deferoxamine, and to a lesser extent by vitamin C. Furthermore, the cold-induced increase in LPO was reduced by C18:0, vitamin E, or DFO but enhanced by DHA. In conclusion, the findings implicate iron catalyzed free radicals and LPO as a predominant mechanism of endothelial cell injury at 0 degrees C, which may be reduced by increasing lipid saturation or treating cells with antioxidants.     

Membrane lipid composition of pancreatic AR42J cells: modification by exposure to different fatty acids

Dietary fat type influences fatty acids in rat pancreatic membranes, in association with modulation of secretory activity and cell signalling in viable acini. We aimed to confirm whether AR42J cells are a valid model to study the interactions between lipids and pancreatic acinar cell function. For this purpose we have (i) compared the baseline fatty acid composition of AR42J cells with that of pancreatic membranes from rats fed a standard chow; (ii) investigated if fatty acids in AR42J membranes can be modified in culture; and (iii) studied if similar compositional variations that can be evoked in rats when dietary fat type is altered occur in AR42J cells. Weaning Wistar rats were fed for 8 weeks either a commercial chow (C) or semi-purified diets containing virgin olive oil (VOO) or sunflower oil (SO) as fat source. AR42J cells were incubated for 72 hrs in medium containing unmodified fetal calf serum (FCS, AR42J-C cells), FCS enriched with 18:1 n-9 (AR42J-O cells), or FCS enriched with 18:2 n-6 (AR42J-L cells). Fatty acids in crude membranes from rat pancreas and AR42J cells were determined by gas-liquid chromatography. Differences in membrane fatty acids between C rats and AR42J-C cells can be explained in part by variations in the amount of fatty acids in the extracellular environment. Supplementation of FCS with 18:1 n-9 or 18:2 n-6 changed the fatty acid spectrum of AR42J cells in a manner that resembles the pattern found, respectively, in VOO and SO rats, although AR42J-L cells were unable to accumulate 20:4 n-6. The AR42J cell line can be a useful tool to assess the effect of membrane compositional changes on acinar cell function. However, differences in baseline characteristics, and perhaps fatty acid metabolism, indicate that results obtained in AR42J cells should be confirmed with experiments in the whole animal.     

Effect of Membrane Polyunsaturation on Carrier-Mediated Transport in Cultured Retinoblastoma Cells: Alterations in Taurine Uptake

Neural cell membranes naturally contain a large amount of polyunsaturated fatty acid, but the functional significance of this is unknown. An increase in membrane polyunsaturation has been shown previously to affect the high-affinity transport systems for choline and glycine in cultured human Y79 retinoblastoma cells. To test the generality of membrane polyunsaturation effects on transport, we investigated the uptake of other putative neurotransmitters and amino acids by these cells. Taurine, glutamate, and leucine were taken up by both high- and low-affinity transport systems, whereas serine, gamma-aminobutyrate, and alpha-aminoisobutyrate were taken up only by low-affinity systems. The high-affinity taurine and glutamate and low-affinity serine uptake systems were Na+ dependent. Arachidonic acid (20:4) supplementation of Y79 cells produced enrichment of all the major microsomal phosphoglycerides with 20:4, while docosahexaenoic acid (22:6) supplementation produced large increases in the 22:6 content of all fractions except the inositol phosphoglycerides. Enrichment with these polyunsaturated fatty acids facilitated taurine uptake by lowering the K'm of its high-affinity transport system. By contrast, enrichment with oleic acid did not affect taurine uptake. Glutamate, leucine, serine, gamma-aminobutyrate, and alpha-aminoisobutyrate uptake were not affected when the cells were enriched with any of these fatty acids. These findings demonstrate that only certain transport systems are sensitive to the polyunsaturated fatty acid content of the retinoblastoma cell membrane. The various transport systems either respond differently to changes in membrane lipid unsaturation, or they are located in lipid domains that are modified to different extents by changes in unsaturation.     

Replacement of the aliphatic chains of Clostridium acetobutylicum by exogenous fatty acids: regulation of phospholipid and glycolipid composition.

The membrane lipid aliphatic chains of Clostridium acetobutylicum ATCC 4259 have been extensively modified by growth in biotin-free medium containing vitamin-free casein hydrolysate supplemented with either elaidic acid, oleic acid, or mixtures of palmitic and oleic acids. Growth with elaidic acid resulted in polar lipids containing 88.6% 18:1 acyl chains and 94.5% 18:1 ether-linked chains. Growth with oleic acid resulted in comparable levels of enrichment of the lipids with 18:1 chains and C19 chains containing cyclopropane rings. When cells were grown with mixtures of palmitic and oleic acids, the ether-linked chains of the plasmalogens were greater than or equal to 64% 18:1 plus C19 chains containing cyclopropane rings at all ratios of oleic to palmitic acid in the medium. The acyl chains reflected the palmitic acid content of the medium more closely. Marked changes were observed in both phospholipid and glycosyldiglyceride compositions as the lipid acyl and ether-linked chains became more enriched with unsaturated and cyclopropane chains. The ratio of the glycerol acetal of plasmenylethanolamine to phosphatidylethanolamine increased, the ratio of cardiolipin to phosphatidylglycerol decreased, and the ratio of diglycosyldiglyceride to monoglycosyldiglyceride increased. However, the monoglycosyldiglyceride/diglycosyldiglyceride ratio was lower for cells grown on 100% oleic acid than for cells grown on 60 or 80% oleic acid. In the membranes of cells grown on 100% oleic acid, the ratio of glycolipids to phospholipids was lower than that found in cells grown on 60% oleic acid. These results indicate that C. acetobutylicum regulates its polar lipid composition in a complex manner involving phospholipids and glycosyldiglycerides. These changes can affect the equilibria between those lipids that form bilayers and those lipids that tend to form nonlamellar phases when enriched with unsaturated aliphatic chains. Phosphoglycolipids of unknown structure were also observed in cells grown either with biotin or with fatty acids. The content of the most abundant phosphoglycolipid also varied with the degree of unsaturation of the cellular lipids.     

Dietary trans fatty acids modulate erythrocyte membrane fatty acyl composition and insulin binding in monkeys

The substitution of trans- for half of the cis-monounsaturated fatty acids in the diet of Macaca fasicularis monkeys resulted in alterations in erythrocyte fatty acid composition and insulin receptor properties but not in membrane fluidity. Both cis and trans diets contained 10% fat and similar fatty acid compositions, except that approximately 50% of the cis-octadecenoate (c-18:1) in the cis diet was replaced with trans-octadecenoate isomers (t-18:1) in the trans diet. Compared with the cis diet, the trans diet resulted in the incorporation of approximately 11% t-18:1, an approximately 50% decrease in c-18:1, an approximately 16% decrease in total saturated fatty acids, and an approximately 20% increase in 18:2(n-6) in erythrocyte membrane lipids. The increase in 18:2(n-6) may reflect on homeostatic mechanisms designed to maintain overall membrane fluidity, as no diet-related changes in fluidity were observed with diphenylhexatriene steady state fluorescence polarization. Values observed for insulin binding and insulin receptor number were higher and binding affinity was lower in monkeys fed the cis diet. In the absence of an effect on overall membrane fluidity, altered receptor activity suggests that insulin receptor activity is dynamic, requiring specific fluid membrane subdomains or highly specific fatty acid-protein interactions.     

Temperature adaptation of biological membranes. The effects of acclimation temperature on the unsaturation of the main neutral and charged phospholipids in mitochondrial membranes of the carp (cyprinus carpio L.)

The phospholipid composition, fatty acid pattern and cholesterol content are studied in mitochondria of red lateral muscle of carp acclimated to high and low environmental temperatures.The results of the experiments are: mitochondria from cold-acclimated carp contain higher proportions of ethanolamine phosphatides than mitochondria from warm-acclimated fish, the opposite is true for the choline phosphatides. Thus, at constant pH, the membrane phospholipids are slightly more negatively charged at low acclimation temperature. The total plasmalogen content is reduced in the cold; this reduction is caused by a decrease in the proportion of the choline plasmalogens. The ethanolamine phosphoglycerides contain approx. 20% of the alk-1-enyl acyl type, irrespective of the acclimation temperature. There is no temperature-dependent difference in the low proportion of cholesterol.The fatty acids of total mitochondrial phospholipids are characterized by large amounts of the $\text{n-3}\text{and}\text{n-6}$ families. The ratio of unsaturated to saturated fatty acids and the unsaturation index are remarkably higher than those reported for comparable mammalian phospholipids. Cold acclimation of carp does not significantly increase the unsaturation of total phospholipids. A fatty acid analysis of the main isolated phospholipids, however, shows that cold acclimation considerably increases unsaturation of the neutral phosphatidylcholine, whereas it dramatically decreases unsaturation of the negatively charged cardiolipin. It is suggested that the observed fatty acid substitution in phosphatidylcholine indicates a temperature-induced fluidity adaptation within the mitochondrial lipid bilayer, whereas the inverse acclimation pattern of cardiolipin provides a suitable lipid to accommodate the temperature-dependent modifications in the dynamic surface shape of integral membrane proteins.     

Lipid composition of isolated epiphyseal cartilage cells, membranes and matrix vesicles.

1. Intact cells, cell fragments (membranes) and matrix vesicles were isolated from the proliferating and calcifying layers of epiphyseal cartilage by sequential hyaluronidase and collagenase digestion and differential centrifugation. Lipids were extracted and analyzed for various lipid classes and their fatty acid composition by column, thin-layer, paper and gas-liquid chromatography. 2. On a protein basis the isolated matrix vesicles had more total lipid than either the membrane or cell fractions, the vesicles and membranes being richer in non-polar lipids and containing smaller quantities of phospholipids than whole cells. Expressed as a percentage of the total lipid, the cells were richer in triacylglycerols and lower in free fatty acids than in the membrane or vesicle fractions. The proportion of free cholesterol and the cholesterol/phospholipid ratio were nearly twice as high in the matrix vesicles as in the other tissue fractions. Choline and ethanolamine phosphoglycerides progressively declined in the membrane and matrix vesicle fractions, whereas serine phosphoglycerides and sphinogomyelin increased. Non-phosphorus-containing polar lipids were present in all fractions, the vesicles being richer in polyhexosyl ceramides, cerebrosides, glycosyldiacylglycerols and certain uncharacterized acidic polar lipids. 3. Fatty acid patterns of the matrix vesicles were distinctive from those of isolated cells, being generally richer in 18 : 0 and 18 : 2, and lower in 16 : 1 and 18 : 1 fatty acids. Monoacyl forms were similarly increased in 16 : 0 and/or 18 : 0, and reduced in 16 : 1, 18 : 1 or 20 : 2 fatty acids, depending on the lipid class. The fatty acid composition of diphosphatidylglycerol from cells and matrix vesicles was markedly different, providing evidence that the cardiolipin in the vesicles was not from mitochondrial components. 4. Based on the fact that the matrix vesicles were significantly enriched in free cholesterol, sphingomyelin, glycolipids and serine-phosphoglycerides, it is concluded that they are derived from the plasma membrane of the cell, supporting earlier conclusions based upon morphological and enzymological evidence.     

Effect of a cholesterol-biosynthesis inhibitor on the fatty acid composition of phospholipids in the serum and tissues of rats

1. Changes produced by a cholesterol-biosynthesis inhibitor, trans-1,4-bis-(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride (AY-9944), in the total fatty acids in the liver and brain, and in phospholipids in the serum, liver, heart, brain and lungs from male rats, have been studied. 2. Treatment with AY-9944 produced the following changes in the fatty acid composition: (a) a marked decrease in the percentage of linoleic acid and an increase in oleic acid in the total fatty acids in the liver; (b) in the serum, an overall decrease in the percentage of linoleic acid in neutral lipids and phospholipids; (c) an increased content of linoleic acid in the beta-acyl chain of phosphatidylcholines in the liver and in sphingomyelins in the brain and lungs; (d) an increased content of palmitic acid and oleic acid in the beta-acyl chain of phosphatidylcholine in the liver, heart and lungs; (e) an increased content of phosphatidylcholines and sphingomyelins, together with an increased percentage of saturated fatty acids in these phosphatides in the lungs. 3. Changes in the phosphatides and the production of foam cells in the lungs suggest that AY-9944 may be of use in the study of the alveolar membrane.