| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom
Experiments were designed to investigate whether leukotriene
(LTB4) receptors can couple directly to phospholipase
A2 (PLA2) in guinea pig eosinophils and the
role of endogenous arachidonic acid (AA) in LTB4-induced
activation of the NADPH oxidase. LTB4 (EC50 
16 nM) and AA (EC50 6 µM) generated hydrogen peroxide
(H2O2) in a concentration-dependent manner and
at an equivalent maximum rate (5–6 nmol/min/106 cells).
LTB4 stimulated PLA2 over a similar
concentration range that activated the NADPH oxidase, although kinetic
studies revealed that the release of [3H]AA
(t1/2 2 s) preceded
H2O2 generation
(t1/2 > 30 s). Pretreatment of
eosinophils with pertussis toxin abolished the increase in
inositol(1,4,5)trisphosphate mass, [Ca2+]c,
[3H]AA release, and H2O2
generation evoked by LTB4. Qualitatively identical results
were obtained in eosinophils in which phospholipase C (PLC) was
desensitized by 4ß-phorbol 12,13-dibutyrate with the exception that
[3H]AA release was largely unaffected. Additional studies
performed with the protein kinase C inhibitor, Ro 31-8220, and under
conditions in which Ca2+ mobilization was abolished,
provided further evidence that LTB4 released
[3H]AA independently of signal molecules derived from the
hydrolysis of phosphatidylinositol(4,5)bisphosphate by PLC.
Pretreatment of eosinophils with the PLA2 inhibitor,
mepacrine, abolished LTB4-induced [3H]AA
release at a concentration that inhibited H2O2
by only 36%. Collectively, the results of this study indicate that
agonism of LTB4 receptors on guinea pig eosinophils
mobilizes AA by a mechanism that does not involve the activation of
PLC. In addition, although LTB4 effectively stimulated
PLA2, a central role for AA in the activation of the NADPH
oxidase was excluded.
This article has been cited by other articles:
|
|
 |
|
  C. H. C. Serezani, D. M. Aronoff, S. Jancar, and M. Peters-Golden Leukotriene B4 mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acid-stimulated neutrophils J. Leukoc. Biol., October 1, 2005; 78(4): 976 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. C. Serezani, D. M. Aronoff, S. Jancar, P. Mancuso, and M. Peters-Golden Leukotrienes enhance the bactericidal activity of alveolar macrophages against Klebsiella pneumoniae through the activation of NADPH oxidase Blood, August 1, 2005; 106(3): 1067 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Thomas, S. L. Kunkel, and N. W. Lukacs Regulation of Cockroach Antigen-Induced Allergic Airway Hyperreactivity by the CXCR3 Ligand CXCL9 J. Immunol., July 1, 2004; 173(1): 615 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Decoursey Voltage-Gated Proton Channels and Other Proton Transfer Pathways Physiol Rev, April 1, 2003; 83(2): 475 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Antczak, P. Montuschi, S. Kharitonov, P. Gorski, and P. J. Barnes Increased Exhaled Cysteinyl-Leukotrienes and 8-Isoprostane in Aspirin-induced Asthma Am. J. Respir. Crit. Care Med., August 1, 2002; 166(3): 301 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Woo, H.-J. You, S.-H. Cho, Y.-W. Eom, J.-S. Chun, Y.-J. Yoo, and J.-H. Kim Leukotriene B4 Stimulates Rac-ERK Cascade to Generate Reactive Oxygen Species That Mediates Chemotaxis J. Biol. Chem., March 1, 2002; 277(10): 8572 - 8578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T E DeCoursey, V V Cherny, A G DeCoursey, W Xu, and L L Thomas Interactions between NADPH oxidase-related proton and electron currents in human eosinophils J. Physiol., September 15, 2001; 535(3): 767 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V V Cherny, L M Henderson, W Xu, L L Thomas, and T E DeCoursey Activation of NADPH oxidase-related proton and electron currents in human eosinophils by arachidonic acid J. Physiol., September 15, 2001; 535(3): 783 - 794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. HANAZAWA, S. A. KHARITONOV, and P. J. BARNES Increased Nitrotyrosine in Exhaled Breath Condensate of Patients with Asthma Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1273 - 1276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. del Pozo, F. Pirotto, B. Cárdaba, I. Cortegano, S. Gallardo, M. Rojo, I. Arrieta, E. Aceituno, P. Palomino, A. Gaya, et al. Expression on human eosinophils of CD148: a membrane tyrosine phosphatase. Implications in the effector function of eosinophils J. Leukoc. Biol., July 1, 2000; 68(1): 31 - 37. [Abstract] [Full Text]
|
|
|
|
|
|
O. T. Lynch, M. A. Giembycz, I. Daniels, P. J. Barnes, and M. A. Lindsay Pleiotropic role of lyn kinase in leukotriene B4-induced eosinophil activation Blood, June 1, 2000; 95(11): 3541 - 3547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Giembycz and M. A. Lindsay Pharmacology of the Eosinophil Pharmacol. Rev., June 1, 1999; 51(2): 213 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Woo, Y.-W. Eom, M.-H. Yoo, H.-J. You, H. J. Han, W. K. Song, Y. J. Yoo, J.-S. Chun, and J.-H. Kim Tumor Necrosis Factor-alpha Generates Reactive Oxygen Species via a Cytosolic Phospholipase A2-linked Cascade J. Biol. Chem., October 6, 2000; 275(41): 32357 - 32362. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
