![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 56, Issue 5, 1055-1062, November 1999
Centre de Recherche en Rhumatologie et Immunologie, Centre de
Recherche du Centre Hospitalier Universitaire de Québec, Pavillon
CHUL and Faculté de Médecine, Université Laval,
Quebec, Canada
We report here that the apparent inability of isolated human
polymorphonuclear leukocytes (PMNs) to efficiently transform arachidonic acid (AA) is the consequence of A2a receptor
engagement by endogenous adenosine accumulating in incubation media.
Indeed, when adenosine is eliminated from PMN suspensions by the
addition of adenosine deaminase, or when cells are incubated with
adenosine A2a receptor antagonists, important quantities
(40-80 pmol/106 cells) of 5-lipoxygenase products are
synthesized by PMN incubated with 1 to 5 µM exogenous AA. The
selective A2a receptor agonist CGS21680 was a very potent
inhibitor of the AA-induced leukotriene (LT) synthesis, showing an
IC50 of ~1 nM. The mechanism of AA-induced stimulation of
LT synthesis observed in the absence of extracellular adenosine was
investigated. In adenosine deaminase-treated PMN, exogenous AA induced
Ca2+ mobilization and the translocation of 5-lipoxygenase
to nuclear structures. A time lag of 20 to 60 s (variable between
PMN preparations) was observed consistently between the addition of AA
and the elevation of intracellular Ca2+ concentration (and
LT synthesis), indicating that AA itself did not trigger the
Ca2+ mobilization in PMN. This AA-induced Ca2+
mobilization, as well as the corresponding 5-lipoxygenase translocation and stimulation of LT synthesis, was blocked efficiently by the LT
synthesis inhibitor MK0591, the LTB4 receptor antagonists
CP105696 and LY223982, and the LTA4 hydrolase inhibitor
SC57461A. These data demonstrate that AA is a highly potent and
effective activator of LT synthesis and acts through a mechanism that
requires an autocrine stimulatory loop by LTB4.
This article has been cited by other articles:
|
|
 |
|
  J. R. Jordan, E. E. Moore, E. L. Sarin, S. S. Damle, S. B. Kashuk, C. C. Silliman, and A. Banerjee Arachidonic acid in postshock mesenteric lymph induces pulmonary synthesis of leukotriene B4 J Appl Physiol, April 1, 2008; 104(4): 1161 - 1166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Fortin, D. Harbour, M. Fernandes, P. Borgeat, and S. Bourgoin Differential expression of adenosine receptors in human neutrophils: up-regulation by specific Th1 cytokines and lipopolysaccharide J. Leukoc. Biol., March 1, 2006; 79(3): 574 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Flamand, J. Lefebvre, M. E. Surette, S. Picard, and P. Borgeat Arachidonic Acid Regulates the Translocation of 5-Lipoxygenase to the Nuclear Membranes in Human Neutrophils J. Biol. Chem., January 6, 2006; 281(1): 129 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Luo, S. M. Jones, S. M. Phare, M. J. Coffey, M. Peters-Golden, and T. G. Brock Protein Kinase A Inhibits Leukotriene Synthesis by Phosphorylation of 5-Lipoxygenase on Serine 523 J. Biol. Chem., October 1, 2004; 279(40): 41512 - 41520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Meksawan, J. T. Venkatraman, A. B. Awad, and D. R. Pendergast Effect of Dietary Fat Intake and Exercise on Inflammatory Mediators of the Immune System in Sedentary Men and Women J. Am. Coll. Nutr., August 1, 2004; 23(4): 331 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, Z. Liu, S. Chuai, and X. Shen Phospholipase C and phosphatidylinositol 3-kinase signaling are involved in the exogenous arachidonic acid-stimulated respiratory burst in human neutrophils J. Leukoc. Biol., September 1, 2003; 74(3): 428 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chen, N. Li, S. Wang, N. Wu, J. Hong, X. Jiao, M. J. Krasna, D. G. Beer, and C. S. Yang Leukotriene A4 Hydrolase in Rat and Human Esophageal Adenocarcinomas and Inhibitory Effects of Bestatin J Natl Cancer Inst, July 16, 2003; 95(14): 1053 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. BOILARD, S. G. BOURGOIN, C. BERNATCHEZ, P. E. POUBELLE, and M. E. SURETTE Interaction of low molecular weight group IIA phospholipase A2 with apoptotic human T cells: role of heparan sulfate proteoglycans FASEB J, June 1, 2003; 17(9): 1068 - 1080. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mayer, S. Gokorsch, C. Fegbeutel, K. Hattar, S. Rosseau, D. Walmrath, W. Seeger, and F. Grimminger Parenteral Nutrition with Fish Oil Modulates Cytokine Response in Patients with Sepsis Am. J. Respir. Crit. Care Med., May 15, 2003; 167(10): 1321 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Grenier, N. Flamand, J. Pelletier, P. H. Naccache, P. Borgeat, and S. G. Bourgoin Arachidonic acid activates phospholipase D in human neutrophils; essential role of endogenous leukotriene B4 and inhibition by adenosine A2A receptor engagement J. Leukoc. Biol., April 1, 2003; 73(4): 530 - 539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Burkert, D. Szellas, O. Radmark, D. Steinhilber, and O. Werz Cell type-dependent activation of 5-lipoxygenase by arachidonic acid J. Leukoc. Biol., January 1, 2003; 73(1): 191 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pouliot, M.-E. Fiset, M. Masse, P. H. Naccache, and P. Borgeat Adenosine Up-Regulates Cyclooxygenase-2 in Human Granulocytes: Impact on the Balance of Eicosanoid Generation J. Immunol., November 1, 2002; 169(9): 5279 - 5286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Flamand, M. E. Surette, S. Picard, S. Bourgoin, and P. Borgeat Cyclic AMP-Mediated Inhibition of 5-Lipoxygenase Translocation and Leukotriene Biosynthesis in Human Neutrophils Mol. Pharmacol., August 1, 2002; 62(2): 250 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Werz, D. Szellas, D. Steinhilber, and O. Radmark Arachidonic Acid Promotes Phosphorylation of 5-Lipoxygenase at Ser-271 by MAPK-activated Protein Kinase 2 (MK2) J. Biol. Chem., April 19, 2002; 277(17): 14793 - 14800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Werz, E. Burkert, B. Samuelsson, O. Radmark, and D. Steinhilber Activation of 5-lipoxygenase by cell stress is calcium independent in human polymorphonuclear leukocytes Blood, February 1, 2002; 99(3): 1044 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. KRAWIEC, J. Y. WESTCOTT, H. W. CHU, S. BALZAR, J. B. TRUDEAU, L. B. SCHWARTZ, and S. E. WENZEL Persistent Wheezing in Very Young Children Is Associated with Lower Respiratory Inflammation Am. J. Respir. Crit. Care Med., May 1, 2001; 163(6): 1338 - 1343. [Abstract] [Full Text]
|
|
|
|
|
|
O. Werz, J. Klemm, B. Samuelsson, and O. Radmark Phorbol ester up-regulates capacities for nuclear translocation and phosphorylation of 5-lipoxygenase in Mono Mac 6 cells and human polymorphonuclear leukocytes Blood, April 15, 2001; 97(8): 2487 - 2495. [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]
|
|
|
|
|
|
T. Yokomizo, K. Kato, H. Hagiya, T. Izumi, and T. Shimizu Hydroxyeicosanoids Bind to and Activate the Low Affinity Leukotriene B4 Receptor, BLT2 J. Biol. Chem., April 6, 2001; 276(15): 12454 - 12459. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
