PMID- 18218859
OWN - NLM
STAT- MEDLINE
DCOM- 20080604
LR  - 20131121
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 83
IP  - 4
DP  - 2008 Apr
TI  - The role of diacylglyceride generation by phospholipase D and phosphatidic acid 
      phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytes.
PG  - 1019-27
LID - 10.1189/jlb.0807531 [doi]
AB  - Diacylglycerides (DAGs) such as 1-oleoyl-2-acetyl-sn-glycerol (OAG) stimulate 
      5-lipoxygenase (5-LO) enzyme activity and function as agonists for human 
      polymorphonuclear leukocytes (PMNL) to induce 5-LO product synthesis. Here, we 
      addressed the role of endogenous DAG generation in agonist-induced 5-LO 
      activation in human PMNL. Preincubation of PMNL with the phospholipase D (PLD) 
      inhibitor 1-butanol potently suppressed 5-LO product synthesis induced by the 
      Ca(2)(+) ionophore A23187 or thapsigargin (TG) and blocked A23187-evoked 
      translocation of 5-LO from the cytosol to the nuclear membrane, analyzed by 
      subcellular fractionation as well as by indirect immunofluorescence microscopy. 
      Tertiary-butanol, a rather poor inhibitor of PLD, caused only moderate 
      suppression of 5-LO and hardly inhibited 5-LO translocation. Interestingly, 
      1-butanol failed to inhibit 5-LO product formation when PMNL were stimulated with 
      OAG (30 microM). Moreover, coincubation of A23187- or TG-stimulated PMNL with OAG 
      reversed inhibition of 5-LO product formation by 1-butanol in a 
      concentration-dependent manner (EC(50), approximately 1 muM) and also restored 
      5-LO translocation. In addition, inhibition of phosphatidic acid phosphatase 
      (PA-P) by propranolol or bromoenol lactone caused suppression of 5-LO product 
      formation and of translocation, which could be reversed by addition of exogenous 
      OAG. Together, our data suggest that in agonist-stimulated PMNL, the endogenous 
      formation of DAGs via the PLD/PA-P pathway determines 5-LO activation.
FAU - Albert, Dana
AU  - Albert D
AD  - Institute of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, 
      Germany.
FAU - Pergola, Carlo
AU  - Pergola C
FAU - Koeberle, Andreas
AU  - Koeberle A
FAU - Dodt, Gabriele
AU  - Dodt G
FAU - Steinhilber, Dieter
AU  - Steinhilber D
FAU - Werz, Oliver
AU  - Werz O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080124
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Diglycerides)
RN  - 0 (Lipoxygenase Inhibitors)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 8PJ61P6TS3 (1-Butanol)
RN  - EC 1.13.11.34 (Arachidonate 5-Lipoxygenase)
RN  - EC 3.1.3.4 (Phosphatidate Phosphatase)
RN  - EC 3.1.4.4 (Phospholipase D)
SB  - IM
MH  - 1-Butanol/pharmacology
MH  - Adult
MH  - Arachidonate 5-Lipoxygenase/*blood
MH  - Calcimycin/pharmacology
MH  - Diglycerides/*metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - Lipoxygenase Inhibitors
MH  - Microscopy, Fluorescence
MH  - Neutrophils/*enzymology
MH  - Phosphatidate Phosphatase/*blood
MH  - Phospholipase D/*blood
MH  - Reference Values
MH  - Thapsigargin/pharmacology
EDAT- 2008/01/26 09:00
MHDA- 2008/06/05 09:00
CRDT- 2008/01/26 09:00
PHST- 2008/01/26 09:00 [pubmed]
PHST- 2008/06/05 09:00 [medline]
PHST- 2008/01/26 09:00 [entrez]
AID - jlb.0807531 [pii]
AID - 10.1189/jlb.0807531 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2008 Apr;83(4):1019-27. doi: 10.1189/jlb.0807531. Epub 2008 Jan 
      24.