Document Detail

Conversion of 5-hydroperoxyeicosatetraenoic acid into leukotriene B4 by rat hepatocytes: a novel cellular source for leukotriene B4.
MedLine Citation:
PMID:  2843745     Owner:  NLM     Status:  MEDLINE    
Rat hepatocyte homogenates converted 5-hydroperoxyeicosatetraenoic acid into leukotriene B4 (LTB4). The reaction was dependent on time and protein and substrate concentration, did not require NADPH or oxygen, and was not supported by heat-inactivated hepatocyte homogenates. The authenticity of the biologically generated LTB4 that eluted at the position of synthetic LTB4 during high performance liquid chromatography was established by UV spectrophotometry, mass spectral analysis, radioimmunoassay, and a LTB4 receptor displacement assay. In addition, a leukotriene bioassay is described in which transient increases in cytosolic Ca2+ within human neutrophils are measured by means of fura-2 fluorescence. Biologically generated LTB4 was 40, 40, and 33% as active as synthetic LTB4 in the radioimmunoassay, receptor displacement assay, and cytosolic calcium bioassay, respectively. This activity is consistent with the biologically derived LTB4 being an epimeric mixture of (5S),(12R)-LTB4 and the much less active (5S),(12S)-LTB4. The formation of LTB4 was inhibited by 5,8,11,14-eicosatetraynoic acid (1 mM), 5,6-dehydro-arachidonic acid (50 microM), propanethiol (1 mM), and O2 (100%) to the extent of 53, 42, 48, and 66%, respectively. No inhibition was observed in the presence of diethylcarbamazine (1 mM) and desferal (1 mM). A possible contribution towards LTB4 formation by contaminating Kupffer cells was excluded (less than 0.2%). These results suggest that hepatocytes can convert lipid peroxides into potent chemoattractants that may alter the homeostasis of immunomediators within the liver.
J Gut; D W Goldman; J R Trudell
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular pharmacology     Volume:  34     ISSN:  0026-895X     ISO Abbreviation:  Mol. Pharmacol.     Publication Date:  1988 Sep 
Date Detail:
Created Date:  1988-10-26     Completed Date:  1988-10-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0035623     Medline TA:  Mol Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  256-64     Citation Subset:  IM    
Department of Anesthesia, Stanford University School of Medicine, California 94305.
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MeSH Terms
Arachidonate 5-Lipoxygenase / antagonists & inhibitors
Arachidonic Acids / metabolism*
Diethylcarbamazine / pharmacology
Leukotriene A4
Leukotriene B4 / biosynthesis*
Liver / metabolism*
Mass Spectrometry
Rats, Inbred Strains
Receptors, Immunologic / analysis
Receptors, Leukotriene B4
Grant Support
Reg. No./Substance:
0/Arachidonic Acids; 0/Leukotriene A4; 0/Leukotrienes; 0/Receptors, Immunologic; 0/Receptors, Leukotriene B4; 71160-24-2/Leukotriene B4; 74581-83-2/arachidonic acid 5-hydroperoxide; 90-89-1/Diethylcarbamazine; EC 5-Lipoxygenase

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