|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 April 2001, Vol. 97, No. 8, pp. 2469-2477
PHAGOCYTES
Activation and priming of neutrophil nicotinamide adenine
dinucleotide phosphate oxidase and phospholipase A2 are
dissociated by inhibitors of the kinases p42ERK2
and p38SAPK and by methyl arachidonyl
fluorophosphonate, the dual inhibitor of cytosolic and
calcium-independent phospholipase A2
Elahe Mollapour,
David C. Linch, and
Pamela J. Roberts
From the Department of Haematology, The Royal Free and
University College, London Medical Schools, London, England.
Arachidonic acid (AA) generated by phospholipase A2
(PLA2) is thought to be an essential cofactor for phagocyte
nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.
Both enzymes are simultaneously primed by cytokines such as
granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor
necrosis factor- (TNF-). The possibility that either
unprimed or cytokine-primed responses of PLA2 or NADPH
oxidase to the chemotactic agents formyl-methionyl-leucyl-phenylalanine (FMLP) and complement factor 5a (C5a) could be differentially inhibited
by inhibitors of the mitogen-activated protein (MAP) kinase family
members p42ERK2 (PD98059) and p38SAPK
(SB203580) was investigated. PD98059 inhibited the activation of
p42ERK2 by GM-CSF, TNF-, and FMLP, but it did not
inhibit FMLP-stimulated superoxide production in either unprimed or
primed neutrophils. There was no significant arachidonate release from
unprimed neutrophils stimulated by FMLP, and arachidonate release
stimulated by calcium ionophore A23187 was not inhibited by PD98059. In
contrast, PD98059 inhibited both TNF-- and GM-CSF-primed
PLA2 responses stimulated by FMLP. On the other hand,
SB203580 inhibited FMLP-superoxide responses in unprimed as well as
TNF-- and GM-CSF-primed neutrophils, but failed to inhibit
TNF-- and GM-CSF-primed PLA2 responses stimulated by
FMLP, and additionally enhanced A23187-stimulated arachidonate
release, showing that priming and activation of PLA2 and
NADPH oxidase are differentially dependent on both the
p38SAPK and p42ERK2 pathways. Studies using C5a
as an agonist gave similar results and confirmed the findings with
FMLP. In addition, methyl arachidonyl fluorophosphonate (MAFP), the
dual inhibitor of c and iPLA2 enzymes, failed to inhibit
superoxide production in primed cells at concentrations that inhibited
arachidonate release. These data demonstrate that NADPH oxidase
activity can be dissociated from AA generation and indicate a more
complex role for arachidonate in neutrophil superoxide production.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Aponte, W. Jiang, M. Lakkis, M.-J. Li, D. Edwards, L. Albitar, A. Vitonis, S. C. Mok, D. W. Cramer, and B. Ye
Activation of Platelet-Activating Factor Receptor and Pleiotropic Effects on Tyrosine Phospho-EGFR/Src/FAK/Paxillin in Ovarian Cancer
Cancer Res.,
July 15, 2008;
68(14):
5839 - 5848.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Morgan, V. V. Cherny, A. Finnegan, J. Bollinger, M. H. Gelb, and T. E. DeCoursey
Sustained activation of proton channels and NADPH oxidase in human eosinophils and murine granulocytes requires PKC but not cPLA2{alpha} activity
J. Physiol.,
March 1, 2007;
579(2):
327 - 344.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. E. Kilpatrick, S. Sun, D. Mackie, F. Baik, H. Li, and H. M. Korchak
Regulation of TNF mediated antiapoptotic signaling in human neutrophils: role of {delta}-PKC and ERK1/2
J. Leukoc. Biol.,
December 1, 2006;
80(6):
1512 - 1521.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Sakamoto, F. Kuribayashi, M. Nakamura, and K. Takeshige
Involvement of p38 MAP Kinase in Not Only Activation of the Phagocyte NADPH Oxidase Induced by Formyl-methionyl-leucyl-phenylalanine but Also Determination of the Extent of the Activity
J. Biochem.,
November 1, 2006;
140(5):
739 - 745.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. R. Sheppard, M. R. Kelher, E. E. Moore, N. J. D. McLaughlin, A. Banerjee, and C. C. Silliman
Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation
J. Leukoc. Biol.,
November 1, 2005;
78(5):
1025 - 1042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Jo, H.-Y. Lee, Y.-N. Lee, J. I. Kim, H.-K. Kang, D.-W. Park, S.-H. Baek, J.-Y. Kwak, and Y.-S. Bae
Group IB Secretory Phospholipase A2 Stimulates CXC Chemokine Ligand 8 Production via ERK and NF-{kappa}B in Human Neutrophils
J. Immunol.,
November 15, 2004;
173(10):
6433 - 6439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Harfi, S. D'Hondt, F. Corazza, and E. Sariban
Regulation of Human Polymorphonuclear Leukocytes Functions by the Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide after Activation of MAPKs
J. Immunol.,
September 15, 2004;
173(6):
4154 - 4163.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Widder, T. Behr, D. Fraccarollo, K. Hu, P. Galuppo, P. Tas, C. E Angermann, G. Ertl, and J. Bauersachs
Vascular endothelial dysfunction and superoxide anion production in heart failure are p38 MAP kinase-dependent
Cardiovasc Res,
July 1, 2004;
63(1):
161 - 167.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Bylund, A. Bjorstad, D. Granfeldt, A. Karlsson, C. Woschnagg, and C. Dahlgren
Reactivation of Formyl Peptide Receptors Triggers the Neutrophil NADPH-oxidase but Not a Transient Rise in Intracellular Calcium
J. Biol. Chem.,
August 15, 2003;
278(33):
30578 - 30586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Zhou, J. Zhao, T. Wiedmer, and P. J. Sims
Normal hemostasis but defective hematopoietic response to growth factors in mice deficient in phospholipid scramblase 1
Blood,
May 13, 2002;
99(11):
4030 - 4038.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
