Document Detail


Selective incorporation of (15S)-hydroxyeicosatetraenoic acid in phosphatidylinositol of human neutrophils: agonist-induced deacylation and transformation of stored hydroxyeicosanoids.
MedLine Citation:
PMID:  2117277     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The uptake and mobilization of (15S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid (15-HETE), a major product of arachidonic acid metabolism, was examined with human neutrophils (polymorphonuclear leukocytes; PMNs). Upon exposure to labeled 15-HETE, PMNs rapidly (15 sec to 20 min) incorporated approximately 20% of the label into phosphatidylinositol, while less than 4% was associated with other phospholipid classes and neutral lipids. This pattern was distinct from that of either labeled arachidonate or labeled(5S)-hydroxy-8,11,14-cis-6-trans-eicosatetraenoic acid (5-HETE), which within 20 min were predominantly associated with triglycerides and phosphatidylcholine. After reversed-phase HPLC, greater than 98% of the label in phosphatidylinositol, isolated from PMNs, was released with phospholipase A2. Upon exposure to either chemotactic peptide (FMLP), phorbol 12-myristate 13-acetate, or an ionophore (A23187), 15-HETE-labeled PMNs released 15-HETE from phosphatidylinositol and displayed an impaired ability to generate leukotriene B4 (LTB4), 20-OH-LTB4, and 20-COOH-LTB4. Deacylated [3H]15-HETE was converted to (5S,15S)-dihydroxy-6,13-trans-8,11-cis-eicosatetraenoic acid (5,15-DHETE), lipoxin A4, and lipoxin B4, each carrying 3H label. PMNs labeled with 5-HETE also released and transformed this HETE when stimulated. However, the profile of labeled products differed between PMNs with either esterified 15-HETE or 5-HETE. When activated, 5-HETE-labeled PMNs generated both 5,20-DHETE and 5,15-DHETE but not labeled lipoxins. Threshold aggregation induced by FMLP with 15-HETE-labeled PMNs was inhibited (approximately 2 orders of magnitude), while the threshold response was relatively unimpaired with either A23187 or phorbol 12-myristate 13-acetate-induced aggregation. Results indicate that 15-HETE is rapidly esterified into phosphatidylinositol of PMNs, which can be mobilized and transformed upon exposure of the cells to a second signal. Moreover, they suggest that eicosanoid intermediates other than arachidonic acid can be stored by cells, released via signal transduction, and oxygenated to generate alternative profiles of eicosanoids.
Authors:
M E Brezinski; C N Serhan
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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:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  87     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1990 Aug 
Date Detail:
Created Date:  1990-09-20     Completed Date:  1990-09-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  6248-52     Citation Subset:  IM    
Affiliation:
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
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MeSH Terms
Descriptor/Qualifier:
Arachidonic Acid
Arachidonic Acids / blood
Biotransformation
Eicosanoids / biosynthesis,  blood
Humans
Hydroxyeicosatetraenoic Acids / blood*
Kinetics
Neutrophils / metabolism*
Phosphatidylinositols / blood*
Phospholipids / biosynthesis,  blood
Radioisotope Dilution Technique
Tritium
Grant Support
ID/Acronym/Agency:
AI26714/AI/NIAID NIH HHS; GM38765/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Eicosanoids; 0/Hydroxyeicosatetraenoic Acids; 0/Phosphatidylinositols; 0/Phospholipids; 10028-17-8/Tritium; 506-32-1/Arachidonic Acid; 73945-47-8/15-hydroxy-5,8,11,13-eicosatetraenoic acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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