Inability of murine peritoneal macrophages to convert linoleic acid into arachidonic acid. Evidence of chain elongation
Various murine macrophage populations synthesize and secrete large amounts of arachidonic acid (20:4n-6) derived eicosanoids (cyclo-oxygenase and lipoxygenase products). These metabolites are known to possess a wide variety of functions with regard to the initiation and regulation of inflammation and tumorigenesis. Because the dietary intake of 20:4n-6 is usually low, tissues are largely dependent upon dietary linoleic acid (18:2n-6) as an initial unsaturated precursor for the biosynthesis of 20:4n-6. The purpose of these experiments was to determine whether resident or responsive murine macrophages possess desaturase and elongase activities capable of in vitro conversion of 18:2n-6 into 20:4n-6. Peritoneal exudate macrophages were purified by adherence and incubated in serum-free medium containing fatty acid-free BSA with (1-14C) 18:2n-6. Approximately 90 to 98% of the (14C)18:2n-6 at 4 and 16 h was recovered in phosphatidylcholine and phosphatidylethanolamine. The metabolism of (14C)18:2n-6 was determined after transesterification and separation of the 14C-fatty acid methyl esters by argentation TLC, reverse phase HPLC, and electron impact gas chromatography/mass spectrometry. Resident and responsive macrophages lacked the capacity to transform (14C)18:2n-6 into 20:4n-6. In addition, prelabeled macrophages incubated with soluble, calcium ionophore A23187 or phorbol myristate, or particulate, zymosan, membrane perturbing agents also lacked delta 6 desaturase activity. All macrophages tested were capable of elongating (14C)18:2n-6 into (14C)20:2n-6. These observations suggest that 20:4n-6, present in macrophage phospholipids, is biosynthesized elsewhere and transported to the macrophage for esterification into the phospholipids. In addition, these findings demonstrate that elongase activity is present in both the resident and responsive peritoneal macrophage.
- Research Organization:
- Univ. of California, Davis (USA)
- OSTI ID:
- 6970425
- Journal Information:
- J. Immunol.; (United States), Vol. 140:7
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ARACHIDONIC ACID
BIOSYNTHESIS
ENZYME ACTIVITY
LINOLEIC ACID
METABOLISM
MACROPHAGES
PHORBOL ESTERS
BIOLOGICAL EFFECTS
TRANSFERASES
BIOLOGICAL FUNCTIONS
CARBON 14 COMPOUNDS
ESTERIFICATION
GAS CHROMATOGRAPHY
LIQUID COLUMN CHROMATOGRAPHY
MASS SPECTROSCOPY
METABOLITES
MICE
PHOSPHOLIPIDS
PRECURSOR
THIN-LAYER CHROMATOGRAPHY
TRACER TECHNIQUES
ZYMOSAN
ANIMAL CELLS
ANIMALS
CARBOXYLIC ACIDS
CARCINOGENS
CHEMICAL REACTIONS
CHROMATOGRAPHY
CONNECTIVE TISSUE CELLS
ENZYMES
ESTERS
FUNCTIONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPIDS
MAMMALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHAGOCYTES
RODENTS
SEPARATION PROCESSES
SOMATIC CELLS
SPECTROSCOPY
SYNTHESIS
VERTEBRATES
550501* - Metabolism- Tracer Techniques
560300 - Chemicals Metabolism & Toxicology