Regulation of the B cell response to T-dependent antigens by classical pathway complement

We observed that retinoic acid, which differentiates the human neuroblastoma SK-N-BE into mature neurons, induced an elevation in levels of polyunsaturated fatty acids, especially arachidonic acid (20:4 n-6). This effect was not induced by phorbol myristate acetate, another differentiating agent. We then explored the effects of retinoic acid on the formation of arachidonic acid and of docosahexaenoic acid from precursors and on the de novo lipid synthesis from acetate at various stages of differentiation, which was assessed by morphological (cell number and neurite outgrowth) and biochemical (protein content and thymidine incorporation) criteria. At 3 days of incubation with retinoic acid, in the n-6 series, total conversion of linoleic acid, especially to 20:3 n-6, was elevated, in association with preferential incorporation of acetate into phospholipids; in contrast, at 8 days, synthesis of 20-carbon polyunsaturated fatty acids declined, in association with enhanced incorporation in triglycerides. In the n-3 series, eicosapentaenoic acid was converted to docosahexaenoic acid in SK-N-BE, but the conversion was not affected by retinoic acid. During the early stage of neuronal differentiation, therefore, enhanced production of 20-carbon polyunsaturated fatty acids from their precursors occurred, and newly formed fatty acids were preferentially incorporated in phospholipids, possibly in association with membrane deposition. When differentiation was completed, arachidonic acid formation and incorporation of acetate in phospholipids and cholesterol declined with enhanced labeling of storage lipids.     

Intrachromosomal localization of aberration breakpoints induced by neutrons and gamma rays in Chinese hamster ovary cells

BACKGROUND: We recently demonstrated that arachidonic:linoleic acid ratio of erythrocytes of essential hypertension patients is greater than normal. OBJECTIVE: To investigate fatty acid composition, capability for adhesion to biological substrate and expression of beta2 integrins of leucocytes obtained from peripheral blood and skin window exudate of essential hypertension patients. DESIGN: Neutrophil activation state was evaluated by reproducing the various conditions occurring in vivo during the life of the cell (i.e. under the 'resting' condition, such as in peripheral blood, and 'primed' condition, such as after transmigration through the endothelium and after administration of specific chemo-attractants). Because both peripheral blood and skin window leucocytes of the subjects were obtained on the same day, we could be sure that there had been no dietary influences on changes in levels of fatty acid. Thus, the observed changes should reliably reflect the metabolic rate of utilization of fatty acids coupled to the activation and migration of cells. RESULTS: Leucocytes from essential hypertension patients were richer in arachidonic acid than were the corresponding cells from normotensive subjects; this difference was also evident for functionally activated skin window leucocytes, in spite of there having been a greater loss of poly-unsaturated fatty acids and arachidonic acid after migration. Moreover, a greater than normal arachidonic acid:linoleic acid ratio was shown for the first time to apply for leucocytes of essential hypertension patients, so extending our previous findings on the erythrocytes. Leucocytes from essential hypertension patients, collected both from peripheral blood and from skin window exudate, proved far more adhesive than the corresponding cells from age-matched and sex-matched controls, but this was not associated with a quantitative hyperexpression of beta2 integrins. CONCLUSIONS: The results suggest that an increase in availability of arachidonic acid in leucocytes could be a further expression of the generalized disturbance of fatty acid levels associated with essential hypertension and that a condition of hyperadhesion of neutrophils could occur spontaneously in vivo during the course of hypertension.     

Uptake of long chain fatty acids by human placental choriocarcinoma (BeWo) cells: role of plasma membrane fatty acid-binding protein

In order to understand the mechanisms by which fatty acids are taken up by the placenta, the uptake of oleic, linoleic, arachidonic, and docosahexaenoic acids by cultured human placental choriocarcinoma (BeWo) cells was examined. Fatty acid uptake by BeWo cells was temperature-dependent and exhibited saturable kinetics. Oleic acid was taken up least and docosahexaenoic acid most by these cells. Moreover, competitive studies of fatty acid uptake by BeWo cells also indicated preferential uptake compared with oleic acid in the order of docosahexaenoic acid, arachidonic acid, and linoleic acid. Western blot analysis demonstrated that BeWo cells express a protein immunoreactive with antibodies to the human placental plasma membrane fatty acid-binding protein (p-FABPpm). Furthermore, pre-treatment of BeWo cells with these antibodies inhibited most of the uptake of docosahexaenoic (64%) and arachidonic acids (68%) whereas oleic acid uptake was inhibited only 32% compared with the controls treated with preimmune serum. These results clearly demonstrate that the pFABPpm may be involved in the preferential uptake of essential fatty acids (EFA) and their long chain polyunsaturated fatty acids (LCPUFA) by these cells. Studies on the distribution of radiolabeled fatty acids in the cellular lipids of BeWo cells showed that docosahexaenoic acid was incorporated mainly in the triacylglycerol fraction, followed by the phospholipid fraction, whereas for arachidonic acid the reverse was true. The preferential incorporation of docosahexaenoic acid into triacylglycerol suggests that triacylglycerol may play an important role in the placental transport of docosahexaenoic acid to the fetal circulation. Together these results demonstrate the preferential uptake of EFA/LCPUFA by BeWo cells that is most probably mediated via the pFABPpm. We thus propose that the p-FABPpm may be involved in the sequestration of maternal plasma LCPUFA by the placenta.     

Influence of a fat-free diet on the content and synthesis of arachidonic acid in the feto-placental unit of the rat

In rats receiving a fat-free food throughout the period of pregnancy, the individual fatty acids of total lipids from placenta, total fetus, maternal and fetal serum were determined quantitatively on day 21/22 of pregnancy. Also, the incorporation of 14C-acetate in vitro into placental fatty acids, divided by the number of double bonds, was measured and the rate of synthesis calculated therefrom. The fat-free diet caused a drastic fall of linoleic acid concentration in maternal serum and all fetal compartments. On the contrary, the amount of arachidonic acid remained almost unchanged in fetal serum and total fetus, and even slightly increased in placenta. In the maternal serum, too, the arachidonic acid concentration remained constant under fat-free diet. The observed concentration changes of single fatty acids in the maternal serum are reflected in all fetal compartments and led to a rise in total fatty acids in all sera and tissues studied. The height of rise decreased in the order: maternal serum less than placenta less than fetal serum less than total fetus. The rate of synthesis for arachidonic acid in placenta was on day 21/22 of pregnancy 0.3 (controls) and 0.5 (fat-free diet) micrometer/100 g placenta and hour, being able to cover the placenta's own need to less than one-third. The results suggest that the protection of the feto-placental unit against arachidonic acid deficiency under fat-free diet of the mother is provided mainly by a constant supply of maternal unit with arachidonic acid under normal conditions has to be ensured essentially by the mother.     

Total fatty acid composition of duck fatty tissues

Total lipids extracted from duck fatty tissues were fractionated on thin layer plates into polar lipids and neutral lipids. Neutral lipids were similarly fractionated into their components. Fatty acid methyl esters from total lipids were fractionated by gas-liquid-chromatography. Results indicated that duck fatty tissues are mostly formed by neutral lipids and that triglycerides comprise the vast majority of neutral lipids. Results also indicated that the major fatty acids in duck lipids are: oleic greater than linoleic greater than stearic greater than palmitoleic. About 73% of all fatty acids present belong to the C-18 series. The unsaturation level for duck lipids is about 73%.     

Net transfer and incorporation of yolk n-3 fatty acids into developing chick embryos

The effect of egg yolk fatty acid composition on the uptake and utilization of essential n-6 and n-3 fatty acids by the developing chick embryo was studied. Eggs were enriched with n-9, n-3, or n-6 fatty acids by incorporating sunflower seed high in oleic acid (C18:1 n-9), flax seed rich in linolenic acid (C18:3 n-3), or sunflower seed high in linoleic acid (C18:2 n-6) into the laying hen diets. Fertile eggs were collected and incubated. The fatty acid composition of eggs and newly hatched chicks were compared. Feeding diets containing flax seed increased (P < .05) total n-3 fatty to 528.4 mg compared with 53.9 and 39.3 mg for eggs from hens fed diets with high oleic acid or regular sunflower seed, respectively. Levels of C18:2 n-6 and monounsaturated fatty acids were higher in eggs from hens fed diets containing regular or high oleic acid sunflower seeds. Dietary fat did not influence the total lipid content of the egg yolk or total lipids of chick tissues. The fatty acid composition of the hatched progeny was significantly altered by egg yolk lipids. However, the percentage incorporation of essential n-6 and n-3 fatty acids into the progeny increased when yolk sources of these fatty acids were low. The developing chick embryo appeared to preferentially take up docosahexaenoic acid and arachidonic acid from the yolk lipids. Evidence also suggests that conversion of C18:2 n-6 and C18:2 n-3 to longer chain n-3 or n-6 fatty acids occurs during the incubation period.     

Paired pulse analysis of ATP and noradrenaline release from sympathetic nerves of rat tail artery and mouse vas deferens: effects of K+ channel blockers

The barrier function of the skin resides in the stratum corneum (SC). This outermost layer consists of protein-rich corneocytes and lipid-rich intercellular domains. These domains form the rate-limiting step for transepidermal water loss and the penetration of substances from the environment. To study the nature of the barrier function, stratum corneum lipid models have been examined with wide-angle X-ray diffraction. A disadvantage of this technique is that it requires bulk quantities of lipid and thus information on variations in the lateral packing cannot be obtained in the microm-range. To the best of our knowledge, this is the first study in which electron diffraction is applied on SC lipid model systems. Using this technique, local structural information was obtained about mixtures prepared from isolated pig ceramides, cholesterol, and long-chain free fatty acids. It appeared that addition of free fatty acids caused a transition from a hexagonal to an orthorhombic packing and that electron diffraction can be applied to distinguish between these two lattices. The results are in good agreement with wide-angle X-ray diffraction data and suggest that application of electron diffraction in skin studies can provide new information on the lipid organization in well-defined areas of the stratum corneum.     

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The fatty acid composition of erythrocytes, platelets, and serum lipids was compared between subjects who had been eating a strict uncooked vegan diet ("living food") for years and omnivore controls. The vegan diet contains equal amounts of fat but more monounsaturated and polyunsaturated and less saturated fatty acids than the mixed diet of the control group. In vegans, the proportion of linoleic acid was greater in all lipid fractions studied. Also, the levels of other n-6 fatty acids were greater, with the exception of arachidonic acid levels, which were similar in most fractions. In erythrocytes, platelets and serum phospholipid fractions, this increase was mainly at the expense of the n-3 fatty acids. The proportions of eicosapentaenoic and docosahexaenoic acid were only 29-36% and 49-52% of those in controls, respectively. In vegans the ratio of n-3 to n-6 fatty acids was only about half that in omnivores. In addition to the lower levels of n-3 fatty acids, the proportions of palmitic and stearic acids were lower in serum cholesteryl esters, triglycerides and free fatty acids of vegans. The proportion of oleic acid was slightly lower only in serum cholesteryl esters and erythrocyte phosphatidylserine. The results show that, in the long term, the vegan diet has little effect on the proportions of oleic and arachidonic acids, whereas the levels of n-3 fatty acids are depressed to very low levels with prolonged consumption of the high linoleic and oleic acid components of this diet.     

Essential fatty acids in the serum and cerebrospinal fluid of multiple sclerosis patients

Statistical evaluation of essential fatty acids (determined by gas chromatography) in the serum and cerebrospinal fluid of patients with definite MS and acute CCT showed marked differences as compared to healthy subjects. It was also evident that the decrease of essential fatty acids in MS patients differed from that of CCT patients. Whereas the fatty acid levels in the serum of MS patients revealed only minor differences as compared to the controls and CCT patients, MS patients did show a clear decrease, especially of linoleic and arachidonic acids, in the CSF. This difference was most pronounced in cholesterol esters in the CSF. One absorption study with safflower oil demonstrated normal enteral absorption of essential fatty acids and the ability to cross the blood-CSF barrier.     

Binocular processes in vernier acuity

The contribution of synthesis and dietary sequestration to the high arachidonate content of the lone star tick, Amblyomma americanum, salivary glands was investigated by assessing the salivary metabolites of various radiolabeled fatty acid substrates administered to partially fed females. A portion of each of the fatty acids studied was incorporated into the fatty acid moiety of the phospholipid fraction. [14C]acetate was metabolized only into myristic, palmitic, palmitoleic, steric, and oleic acids. [3H]oleic acid, [14C]linoleic acid, [14C]gamma-linolenic acid and [14C]eicosatrienoic acids were incorporated into salivary gland phospholipids but underwent little change including elongation and/or desaturation to arachidonate. Ingested [3H]arachidonic acid was readily taken up by the salivary gland and distributed among the lipid classes in a pattern markedly different from that of the other fatty acids tested. We conclude that ticks are unable to synthesize arachidonic acid for incorporation into the salivary glands, but rather sequester it from the host bloodmeal.     

Desethylamiodarone prolongation of cardiac repolarization is dependent on gene expression: a novel antiarrhythmic mechanism

BACKGROUND/AIMS: Defective platelet aggregation and reduced platelet production of thromboxane A2, a metabolite of arachidonic acid, are common findings in patients with cirrhosis. We evaluated the effects of dietary supplementation with two combinations of unsaturated fatty acids on platelet function and plasma and membrane fatty acids in patients with liver cirrhosis. METHODS: In a double-blind study, 15 patients with cirrhosis and defective aggregation were randomized to receive a 6-week supplementation with gamma-linolenic and linoleic acid (1 g/day of each fatty acid) or with oleic acid and linoleic acid (groups GLA and OA, respectively). RESULTS: Under baseline conditions, patients showed elevated concentrations of monounsaturated fatty acids and a reduction in polyunsaturated fatty acids. The product/precursor ratios for delta6 and delta5 desaturases, two key enzymes in the pathway leading to arachidonic acid, were significantly reduced in the group of patients. In the GLA group, a significant increase in the levels of dihomo-gamma-linolenic acid (20:3omega6) was observed in plasma and membranes, together with a parallel decrease in the 20:4/20:3omega6 ratio after supplementation. No significant changes were observed in the OA group. The levels of arachidonic acid did not change significantly in either group of patients. Platelet aggregation to collagen was unchanged in the GLA group, but significantly improved in the OA group. CONCLUSIONS: These results show that supplementation with precursors of arachidonic acid is ineffective in elevating plasma or membrane arachidonate levels and does not improve platelet aggregation, suggesting that synthesis of arachidonic acid through the delta5 desaturase cannot be correspondingly activated or that incorporation/retention of the produced fatty acid into lipids is impaired. The increased platelet aggregation in the OA group is likely to be explained by the effect of oleic acid contained in the diet, the effects of which may have been counteracted by the elevation in 20:3omega6, a source of anti-aggregatory prostanoids, in the GLA group.     

Systemic vascular resistance in intradialytic hypotension determined by means of impedance cardiography

Topical corticosteroids (TCS) are among the most frequently used topical therapeutics. Recently, it has been shown that TCS not only has antiproliferative actions, but also inhibits the differentiation of the epidermis and finally perturbates stratum corneum (s.c.) barrier function. It is well established that epidermal barrier function resides within the intercellular lipids of the SC. However, to date, little is known about the effects of TCS on the structure and composition of s.c. lipids. We therefore used hairless mouse skin to study the sequential changes of the s.c. permeability barrier and their intercellular lipids by ruthenium tetroxide staining and high-performance thin-layer chromatography (HPTLC) during topical use of corticosteroids. The results demonstrated a progressive increase in transepidermal water loss accompanied by a diminution in the SC intercellular lipid lamellae, which showed a normal structure of individual lamella. Analysis of lipid composition by HPTLC after a 6-week application of TCS also showed an obvious decrease in all the main components of s.c. lipids, which are known to constitute the permeability barrier of the skin. In light of these results, our work provides direct morphological evidence that TCS deteriorates the permeability barrier of epidermis when applied to normal skin.     

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Recent work in our lab has shown that the chemoprotective fatty acid, conjugated linoleic acid (CLA), inhibits phorbol ester skin tumor promotion in mice. Because little is known about the deposition of CLA into tissues as well as its biological activity, this study compared the incorporation and biological activity of CLA to linoleic acid (LA; 18:2, c9,c12) and arachidonic acid (AA; 20:4 c5,c8,c11,c14) in cultured keratinocytes. When keratinocytes (HEL-30) were grown in media containing 14C-CLA for various periods, more than 50% of the 14C-CLA was incorporated into cellular lipids by 9 h. The distribution of CLA in phospholipid classes was similar to LA, Approximately 50% of 14C-LA and 14C-CLA were incorporated into phosphatidylcholine (PC), while the remainder was taken up by phosphatidylethanolamine (PE) and phosphatidylserine/phosphatidylinositol (PS/PI). In contrast, 14C-AA was more equitably distributed into PC, PE, or PS/PI (27, 30, or 38%, respectively). When keratinocytes were prelabeled with radiolabeled fatty acids, phorbol ester-induced release of 14C-CLA was 1.5 times higher than 14C-LA and 14C-AA. However, 14C-prostaglandin E (PGE) release in 14C-CLA prelabeled cultures was 6 and 13 times lower than cultures treated with 14C-LA and 14C-AA, respectively. Moreover, the ability of non-radiolabeled CLA to support ornithine decarboxylase activity, a hallmark event of tumor promotion, was significantly lower than in LA- and AA-treated cultures. These studies suggest that CLA inhibits skin tumor promotion, in part, through a PGE-dependent mechanism.     

Diet-induced changes in the fatty acid composition of mouse hepatocyte plasma membranes

Hepatocyte plasma membranes were isolated from the livers of mice fed either a low fat diet or high fat diets containing polyunsaturated or saturated fat. The combined rate and isopycnic ultracentrifugation technique which was used produced highly purified hepatocyte plasma membrane fractions. The efficacy of the procedure was checked by electron microscopy and the assay to marker enzymes for the different subcellular organelles. Mice were maintained on a low fat diet until 60-70 days of age, when they were fed high fat diets containing polyunsaturated fat. The hepatocyte plasma membrane lipids of mice fed the polyunsaturated fat diet for 4 wk contained increased proportions of the major dietary unsaturated fatty acid, linoleic acid, and increased proportions of arachidonic acid. The proportion of linoleic and arachidonic acids decreased with continued feeding of the polyunsaturated fat diet. The hepatocyte plasma membrane lipids of mice fed the saturated fat diet contained increased proportions of oleic acid.     

Renal insufficiency in the neonatal period

The fatty acid composition of plasma membranes in the placenta of induced-pregnancy females with ovarian hypofunction was studied Palmitic, stearic, and oleic acids were prevalent in the placental membranes. The content of arachidonic acid was higher that of linoleic acid which was in greater qualities in the membranous lipids of other tissues than arachidonic acid. The changes found in the fatty acid composition of placental membranous phospholipids were associated with the deviations in the levels of this organ-specific hormones progesterone and placental lactogen.     

Fatty acids stimulate trehalose synthesis in trophocytes of the cockroach (Periplaneta americana) fat body

Trophocytes from the disaggregated fat body of the cockroach (Periplaneta americana) respond to synthetic hypertrehalosemic hormone (HTH) by increasing the rate of trehalose synthesis. The cells give a similar response when incubated with stearic, oleic, linoleic, or arachidonic acid. A maximal increase in trehalose synthesis was obtained with 1-10 microM fatty acids. Synthesis of trehalose by the trophocytes was also increased by 1 microM prostaglandin F2alpha to nearly the same extent as that evoked by HTH. Furthermore, the data show that the trophocytes are capable of converting linoleic acid into arachidonic acid. This suggests that the cells may convert arachidonic acid, formed from the linoleic acid released by the action of HTH, to a prostaglandin which serves as an integral part of the hypertrehalosemic mechanism.     

The dynamic changes in the fatty acid composition of the sweat from patients in the acute period of a myocardial infarct

Sweat lipids higher fatty acid composition was measured in patients in the time course of myocardial infarction development using a gas-chromatography technique. Within 2-4 days of the onset of myocardial infarction running a complicated course sweat lipids total polyunsaturated fatty acids have gotten strikingly increased (by 700% versus control) at the expense of linoleic acid (a rise by 300%) and arachidonic acid (an increase by 400%), which fact can be relied upon in prognostication and early diagnosis of pulmonary edema and pneumonia.     

Dietary nucleotides correct plasma and liver microsomal fatty acid alterations in rats with liver cirrhosis induced by oral intake of thioacetamide

BACKGROUND/AIMS: Dietary nucleotides modulate a number of metabolic processes, including long-chain polyunsaturated fatty acid metabolism. In this study, we evaluated the effect of dietary nucleotides on plasma and liver microsomal fatty acid profiles in a rat model of liver cirrhosis induced by oral intake of thioacetamide. METHODS: Fifty-four female Wistar rats were assigned to one of the following groups: rats in the thioacetamide group (n=45) were given 300 mg thioacetamide/l in their drinking water for 4 months, and rats in the control group (n=9) received water during the same period. After 4 months of treatment, 9 rats in each group were killed. The remaining rats in the thioacetamide group were divided into two new groups, and the animals in each were allowed to recover for 1 or 2 weeks on either a nucleotide-free diet or the same diet supplemented with 50 mg of each of the following: AMP, GMP, CMP, IMP and UMP per 100 g diet. RESULTS: Saturated (mainly stearic acid), monounsaturated, and n-6 long-chain polyunsaturated fatty acids (mainly arachidonic acid), and also the unsaturation index decreased in plasma of rats with experimental cirrhosis. Administration of the diet supplemented with nucleotides to thioacetamide-treated rats corrected plasma levels of saturated, n-6 long-chain polyunsaturated fatty acids and the unsaturation index. In liver microsomes, the cirrhotic rats showed lower levels of protein and higher levels of palmitic, oleic, linoleic and arachidonic acids. Protein concentrations and levels of all the above-mentioned fatty acids were corrected with the nucleotide-enriched diet. CONCLUSIONS: Dietary nucleotides contribute to correcting plasma and liver microsomal fatty acid alterations in rats with liver cirrhosis induced by chronic oral administration of thioacetamide.     

A new HPLC-based method for the quantitative analysis of inner stratum corneum lipids with special reference to the free fatty acid fraction

The inner stratum corneum is likely to represent the location of the intact skin barrier, unperturbed by degradation processes. In our studies of the physical skin barrier a new high-performance liquid chromatography (HPLC)-based method was developed for the quantitative analysis of lipids of the inner stratum corneum. All main lipid classes were separated and quantitated by HPLC/light scattering detection (LSD) and the free fatty acid fraction was further analysed by gas-liquid chromatography (GLC). Mass spectrometry (MS) was used for peak identification and flame ionization detection (FID) for quantitation. Special attention was paid to the free fatty acid fraction since unsaturated free fatty acids may exert a key function in the regulation of the skin barrier properties by shifting the physical equilibrium of the multilamellar lipid bilayer system towards a noncrystalline state. Our results indicated that the endogenous free fatty acid fraction of the stratum corneum barrier lipids in essence exclusively consisted of saturated long-chain free fatty acids. This fraction was characterized as a very stable population (low interindividual peak variation) dominated by saturated lignoceric acid (C24:0, 39 molar%) and hexacosanoic acid (C26:0, 23 molar%). In addition, trace amounts of very long-chain (C32-C36) saturated and monounsaturated free fatty acids were detected in human forearm inner stratum corneum. Our analysis method gives highly accurate and precise quantitative information on the relative composition of all major lipid species present in the skin barrier. Such data will eventually permit skin barrier model systems to be created which will allow a more detailed analysis of the physical nature of the human skin barrier.     

Linoleic acid enhances the secretion of plasminogen activator inhibitor type 1 by HepG2 cells

This study was undertaken in order to assess whether triglycerides and/or their fatty acids directly influence the secretion of plasminogen activator inhibitor type 1 (PAI-1) in HepG2 cells. To this end, subconfluent HepG2 cells were incubated with triglyceride-rich particles (TGRP) isolated from Intralipid for 16 h, and PAI-1 levels were determined in conditioned medium using a specific ELISA. TGRP (1 to 6 mg triglycerides/ml) concentration-dependently increased PAI-1 secretion by cells, concomitantly with significant increases in intracellular triglyceride (TG) levels. Fatty acid analysis indicated that the incubation of cells with 3 mg of TG per ml of TGRP induced significant accumulation of 18:2 n-6 (linoleic acid, LA) and 18:3 n-3 (linolenic acid) reflecting the fatty acid composition at the added triglycerides. We then tested the comparative effects on PAI-1 secretion by HepG2 cells of LA and 18:1 n-9 (oleic acid, OA). LA, as a bovine serum albumin (BSA) complex, concentration-dependently (1 to 35 mumol/L) increased the secretion of PAI-1 by cells, whereas OA-BSA only minimally affected it at the highest concentration used (35 mumol/L). Incorporation of LA into cell pools, in the presence of increasing concentration of the FA in the medium, was studied by the use of a preparation containing [14C]LA. LA accumulated in all lipid classes including diacylglycerol, the incorporated LA being converted into arachidonic acid (AA) as assessed by HPLC radiochromatography of the fatty acid methyl esters. It is concluded that PAI-1 secretion in HepG2 cells is modulated by triacylglycerols and by linoleic acid and/or its metabolic products.