Production of arachidonic and linoleic acid metabolites by guinea pig tracheal epithelial cells (original) (raw)
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Incorporation of α-linolenic acid and linoleic acid into human respiratory epithelial cell lines
Lipids, 2001
Animal and human studies designed to examine the effects of α-linolenic acid (ALA) and linoleic acid (LA) supplementation on the fatty acid composition of plasma and tissues have demonstrated a marked difference in incorporation into phospholipids of these 18-carbon precursors of the longchain polyunsaturates. Whereas tissue phospholipid levels are linearly related to dietary ALA and LA, the levels of tissue LA can be 10-fold higher than tissue ALA even when dietary levels are equivalent. There is some dispute whether this disparity is due to ALA being more rapidly metabolized to its products or substantially oxidized by the liver, or whether LA but not ALA is readily incorporated into cellular phospholipids. We examined the level of incorporation of polyunsaturated fatty acids into human respiratory epithelial cell lines (A549, 16HBE) by determining the dose-dependent incorporation of ALA and LA as free fatty acid (5-150 µg FFA/mL). Cell membrane phospholipid ALA and LA were both increased up to ~20-30% total fatty acids, with a concomitant decrease predominantly in monounsaturated membrane fatty acids, before significant toxicity was observed (50 µg/mL). Our data support the concept that rather than any inherent inability by human cells to incorporate ALA into membrane phospholipids, the lack of ALA content in human and animal tissues in vivo is due to the rapid metabolism or oxidation of this fatty acid in the liver.
AJP: Lung Cellular and Molecular Physiology, 2010
Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o− sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr−/− transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage f...
Iranian Journal of Basic Medical Sciences, 2019
Objective(s): The effects of alpha linolenic acid (ALA) on tracheal responsiveness (TR), total protein (TP), phospholipase A2 (PLA2), immunoglobulin E (IgE), interleukin 4 (IL-4), interferon gamma (INF-γ) level and INF-γ/IL4 ratio in bronchoalveolar lavage fluid (BALF) of sensitized rats were examined. Materials and Methods: TR to methacholine and ovalbumin (OA), BALF levels of TP, PLA2 and IgE as well as IL-4, INF-γ and INF-γ/IL4 ratio were measured in control group (non-sensitized, group C), sensitized rats to OA (group S), S groups treated with two concentrations of ALA and dexamethasone group. Results: TR to methacholine and OA, BALF levels of TP, PLA2, IgE and IL-4 were significantly increased but BALF level of INF-γ and INF-γ/IL4 ratio decreased in group S compared to group C (P<0.001 for all cases). Treated S groups with dexamethasone and both concentrations of ALA lead to significant decrease in TR to methacholine and OA, BALF levels of TP, PLA2, IgE and IL-4 compared to ...
Journal of Allergy and Clinical Immunology, 1995
The influence of 13-hydroxy-linoleic acid (13-HODE) on the pulmonary resistance and dynamic compliance of guinea pigs in vivo was determined. Intravenously administered histamine and methacholine caused dose-dependent increases in pulmonary resistance and dose-dependent decreases in dynamic compliance in anesthetized, spontaneously breathing guinea pigs. Inhalation of an aerosol containing 13-HODE (10 mumol/L) enhanced the increases in pulmonary resistance observed after administration of histamine or methacholine when compared with the respective control animals. The effect of 13-HODE on the increase in pulmonary resistance after administration of histamine was dose-dependent. An enhancement in the pulmonary resistance was already measured after treatment of guinea pigs with aerosols of solutions containing 0.1 mumol/L 13-HODE when compared with that of control animals. In contrast, the changes in dynamic compliance were not affected by 13-HODE. These results indicate that 13-HODE may play an important role in the induction of airway hyperresponsiveness in vivo when it is produced or released in significant amounts in the airways.
Intestinal conversion of linoleic acid to arachidonic acid in the rat
The Journal of Nutritional Biochemistry, 1993
The arachidonic acid (C20:4, n-6) appearing in intestinal lymph during linoleic acid (C18:2, n-6) absorption may originate from enterocyte synthesis or from the liver either after secretion in biliary phospholipids at the same time dietary linoleic acid absorption occurs or via plasma. The radioactivity measured in the total bile collected during the 6 hours of linoleic acid absorption is too small to explain hepatic origin of the C20:4 detected by high performance liquid chromatography analysis of labeled fatty acids recovered in the lymph, in the intestinal mucosa, and the intestinal wall at the peak of linoleic acid intestinal absorption. This study confirms the probability that under in vivo conditions, during the absorption processes, rat intestine is able to convert dietary linoleic acid independent of liver desaturases and elongase activities. (J. Nutr. Biochem. 4:655-658, 1993.)
Linoleic acid metabolite drives severe asthma by causing airway epithelial injury
Scientific reports, 2013
Airway epithelial injury is the hallmark of various respiratory diseases, but its mechanisms remain poorly understood. While 13-S-hydroxyoctadecadienoic acid (13-S-HODE) is produced in high concentration during mitochondrial degradation in reticulocytes little is known about its role in asthma pathogenesis. Here, we show that extracellular 13-S-HODE induces mitochondrial dysfunction and airway epithelial apoptosis. This is associated with features of severe airway obstruction, lung remodeling, increase in epithelial stress related proinflammatory cytokines and drastic airway neutrophilia in mouse. Further, 13-S-HODE induced features are attenuated by inhibiting Transient Receptor Potential Cation Channel, Vanilloid-type 1 (TRPV1) both in mouse model and human bronchial epithelial cells. These findings are relevant to human asthma, as 13-S-HODE levels are increased in human asthmatic airways. Blocking of 13-S-HODE activity or disruption of TRPV1 activity attenuated airway injury and ...
Arachidonic acid metabolism in bovine alveolar macrophages
Inflammation, 1986
The production of lipoxygenase metabolites of arachidonic acid was studied in bovine alveolar macrophages (BAM). Unstimulated macrophages produced sinai1 amounts of LTB4 (0.2 + 0.2 ng/106 BAM) but monohydroxyeicosatetraenoic acids (5-, 12-, and 15-HETE) usually were not detectable. Both exogenous arachidonic acid and the calcium ionophore A23187 induced production of LTB 4, 5~, 12-, and 15-HETE, of which 60-80% was 5-HETE. Combined challenge of BAM with both exogenous al~chidonic acid and A23187 was more effective in the production of these metabolites than with either stimulus alone. The generation of the peptidoleukotfienes LTC4, LTD4, and LTE4 by BAM could not be detected under these in vitro conditions. Our results demonstrate that bovine alveolar macrophages produce similar lipoxygenase metabolites of arachidonic acid in response to A23187, as do human alveolar macrophages stimulated with the same agonist.
Prostaglandins Leukotrienes and Essential Fatty Acids, 2000
We investigated the fatty acid distribution in guinea pig alveolar apical membranes at different developmental stages. Fatty acid composition of the purified membranes isolated from guinea pig fetuses (at 65 day, term=68 day), neonates (day 1) and adult males was determined. The levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) were higher in the adult guinea pig alveolar apical membrane phosphatidylethanolamine (PE) fraction (9.3±2.2 and 2.9±1.0%, respectively) while in other phospholipids (PL) fractions their levels were low or absent (P<0.01). Furthermore, levels of AA and DHA in the PE fraction of apical membrane increased significantly from fetal (6.6±3.0 and 0.8±0.4%, respectively) to neonatal life (10.3±1.5 and 3.0±0.8%, respectively). Increase in the level of DHA (almost four-fold) was much more pronounced than that of AA (P<0.05). As for guinea pig alveolar membranes, EPA and AA were mostly present in the PE fraction in pulmonary adenocarcinoma derived cells (A549 cells), a parallel model of type II pneumocytes, with the levels of AA around three-fold greater than that of EPA, Binding of radiolabelled fatty acids to A549 cells showed no significant differences between the maximum uptake achieved for different fatty acids (AA, 1.7±0.2, EPA, 2.3±0.3, LA, 1.7±0.2, OA, 2.0±0.2nmol/mg protein, P>0.5). Once the fatty acids were taken up by these cells AA was mostly identifiable in the monoacylglycerol (MAG) fraction, whereas EPA was equally distributed between the MAG and PL fractions. Oleic acid was mainly present in the triglyceride (TAG) fraction whereas LA was evenly distributed between the TAG, MAG, and PL fractions. Our data demonstrate a preferential distribution of AA and DHA in PE fractions of alveolar apical membranes during development.
Lipid metabolites as regulators of airway smooth muscle function
Pulmonary Pharmacology & Therapeutics, 2009
Compelling evidence identifies airway smooth muscle (ASM) not only as a target but also a cellular source for a diverse range of mediators underlying the processes of airway narrowing and airway hyperresponsiveness in diseases such as asthma. These include the growing family of plasma membrane phospholipid-derived polyunsaturated fatty acids broadly characterised by the prostaglandins, leukotrienes, lipoxins, isoprostanes and lysophospholipids. In this review, we describe the enzymatic and non-enzymatic biosynthetic pathways of these lipid mediators and how these are influenced by drug treatment, oxidative stress and airways disease. Additionally, we outline their cognate receptors, many of which are expressed by ASM. We describe potential deleterious and protective roles for these lipid mediators in airway inflammatory and remodelling processes by describing their effects on diverse functions of ASM in asthma that have the potential to contribute to asthma pathogenesis and symptoms. These functions include contractile tone development, cytokine and extracellular matrix production, and cellular proliferation and migration.