Document Detail

Potential phospholipid source(s) of arachidonate used for the synthesis of leukotrienes by the human neutrophil.
MedLine Citation:
PMID:  2539804     Owner:  NLM     Status:  MEDLINE    
The present study has employed two approaches to address the question of whether there are specific phospholipid sources of arachidonate used for leukotriene biosynthesis in the human neutrophil. Firstly, g.c.-m.s. analysis indicated that arachidonate was lost from all major arachidonate-containing phospholipid subclasses during cell activation with ionophore A23187. On a molar basis, the rank order of breakdown among the three major phospholipids was: 1-alk-1-enyl-2-arachidonoyl-sn-glycero-3-phosphoethanolamine greater than 1-alkyl-2-arachidonoyl-sn-3-phosphocholine greater than 1-acyl-2-arachidonyl-sn-3-phosphoinositol. Leukotrienes released into the supernatant fluid accounted for only 10-35% of the total arachidonate depletion. Phospholipid sources were also identified in labelling experiments where the specific radioactivity of arachidonate in phospholipid subclasses, as well as leukotrienes produced during cell activation, was measured. The specific radioactivity of arachidonate within 1-acyl-linked molecular species of phosphatidylcholine and phosphatidylinositol was initially high relative to the leukotrienes and decreased rapidly with stimulation. By contrast, the specific radioactivity of arachidonate in all three subclasses of phosphatidylethanolamine, 1-acyl, 1-alkyl, and 1-alk-1-enyl, was 3-5-fold below that of the leukotrienes throughout cell activation. Of the six major arachidonate-containing subclasses, only in the case of 1-O-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine did the specific radioactivity correlate well with that of leukotriene B4 and 20-hydroxyleukotriene B4. These data strongly suggest that 1-ether-linked phospholipids are an important source of arachidonate used for leukotriene biosynthesis.
F H Chilton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Biochemical journal     Volume:  258     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1989 Mar 
Date Detail:
Created Date:  1989-05-23     Completed Date:  1989-05-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  327-33     Citation Subset:  IM    
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21239.
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MeSH Terms
Arachidonic Acid
Arachidonic Acids / metabolism*
Calcimycin / pharmacology
Eicosanoic Acids / metabolism
Leukotriene B4 / biosynthesis
Leukotrienes / biosynthesis*
Neutrophils / drug effects,  metabolism*
Phospholipids / metabolism*
Tritium / diagnostic use
Grant Support
Reg. No./Substance:
0/Arachidonic Acids; 0/Eicosanoic Acids; 0/Leukotrienes; 0/Phospholipids; 10028-17-8/Tritium; 506-32-1/Arachidonic Acid; 52665-69-7/Calcimycin; 71160-24-2/Leukotriene B4

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