PMID- 2117277
OWN - NLM
STAT- MEDLINE
DCOM- 19900920
LR  - 20220408
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 87
IP  - 16
DP  - 1990 Aug
TI  - Selective incorporation of (15S)-hydroxyeicosatetraenoic acid in 
      phosphatidylinositol of human neutrophils: agonist-induced deacylation and 
      transformation of stored hydroxyeicosanoids.
PG  - 6248-52
AB  - 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.
FAU - Brezinski, M E
AU  - Brezinski ME
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, MA.
FAU - Serhan, C N
AU  - Serhan CN
LA  - eng
GR  - AI26714/AI/NIAID NIH HHS/United States
GR  - GM38765/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Arachidonic Acids)
RN  - 0 (Eicosanoids)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Phosphatidylinositols)
RN  - 0 (Phospholipids)
RN  - 10028-17-8 (Tritium)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 73945-47-8 (15-hydroxy-5,8,11,13-eicosatetraenoic acid)
SB  - IM
MH  - Arachidonic Acid
MH  - Arachidonic Acids/blood
MH  - Biotransformation
MH  - Eicosanoids/biosynthesis/blood
MH  - Humans
MH  - Hydroxyeicosatetraenoic Acids/*blood
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Neutrophils/*metabolism
MH  - Phosphatidylinositols/*blood
MH  - Phospholipids/biosynthesis/blood
MH  - Radioisotope Dilution Technique
MH  - Tritium
PMC - PMC54510
EDAT- 1990/08/01 00:00
MHDA- 1990/08/01 00:01
PMCR- 1991/02/01
CRDT- 1990/08/01 00:00
PHST- 1990/08/01 00:00 [pubmed]
PHST- 1990/08/01 00:01 [medline]
PHST- 1990/08/01 00:00 [entrez]
PHST- 1991/02/01 00:00 [pmc-release]
AID - 10.1073/pnas.87.16.6248 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1990 Aug;87(16):6248-52. doi: 10.1073/pnas.87.16.6248.