help button home button Am J Pathol ASIP MEMBERSHIP
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gronert, K.
Right arrow Articles by Serhan, C. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gronert, K.
Right arrow Articles by Serhan, C. N.
(American Journal of Pathology. 2001;158:3-9.)
© 2001 American Society for Investigative Pathology

Short Communications

Selectivity of Recombinant Human Leukotriene D4, Leukotriene B4, and Lipoxin A4 Receptors with Aspirin-Triggered 15-epi-LXA4 and Regulation of Vascular and Inflammatory Responses

Karsten Gronert, Titti Martinsson-Niskanen, Saula Ravasi, Nan Chiang and Charles N. Serhan

From the Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Perioperative and Pain Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts

Aspirin-triggered lipoxin A4 (ATL, 15-epi-LXA4) and leukotriene D4 (LTD4) possess opposing vascular actions mediated via receptors distinct from the LXA4 receptor (ALX) that is involved in leukocyte trafficking. Here, we identified these receptors by nucleotide sequencing and demonstrate that LTD4 receptor (CysLT1) is induced in human vascular endothelia by interleukin-1ß. Recombinant CysLT1 receptor gave stereospecific binding with both [3H]-LTD4 and a novel labeled mimetic of ATL ([3H]-ATLa) that was displaced with LTD4 and ATLa (~IC50 0.2 to 0.9 nmol/L), but not with a bioinactive ATL isomer. The clinically used CysLT1 receptor antagonist, Singulair, showed a lower rank order for competition with [3H]-ATLa (IC50 {approx} 8.3 nmol/L). In contrast, LTD4 was an ineffective competitive ligand for recombinant ALX receptor with [3H]-ATLa, and ATLa did not compete for [3H]-LTB4 binding with recombinant LTB4 receptor. Endogenous murine CysLT1 receptors also gave specific [3H]-ATLa binding that was displaced with essentially equal affinity by LTD4 or ATLa. Systemic ATLa proved to be a potent inhibitor (>50%) of CysLT1-mediated vascular leakage in murine skin (200 µg/kg) in addition to its ability to block polymorphonuclear leukocyte recruitment to dorsal air pouch (4 µg/kg). These results indicate that ATL and LTD4 bind and compete with equal affinity at CysLT1, providing a molecular basis for aspirin-triggered LXs serving as a local damper of both vascular CysLT1 signals as well as ALX receptor-regulated polymorphonuclear leukocyte traffic.




This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
R. Medeiros, G. B. Rodrigues, C. P. Figueiredo, E. B. Rodrigues, A. Grumman Jr., O. Menezes-de-Lima Jr., G. F. Passos, and J. B. Calixto
Molecular Mechanisms of Topical Anti-Inflammatory Effects of Lipoxin A4 in Endotoxin-Induced Uveitis
Mol. Pharmacol., July 1, 2008; 74(1): 154 - 161.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. G. Souza, C. T. Fagundes, F. A. Amaral, D. Cisalpino, L. P. Sousa, A. T. Vieira, V. Pinho, J. R. Nicoli, L. Q. Vieira, I. M. Fierro, et al.
The Required Role of Endogenously Produced Lipoxin A4 and Annexin-1 for the Production of IL-10 and Inflammatory Hyporesponsiveness in Mice
J. Immunol., December 15, 2007; 179(12): 8533 - 8543.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
B. D. Levy, N. W. Lukacs, A. A. Berlin, B. Schmidt, W. J. Guilford, C. N. Serhan, and J. F. Parkinson
Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism
FASEB J, December 1, 2007; 21(14): 3877 - 3884.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. Parameswaran, K. Radford, A. Fanat, J. Stephen, C. Bonnans, B. D. Levy, L. J. Janssen, and P. G. Cox
Modulation of Human Airway Smooth Muscle Migration by Lipid Mediators and Th-2 Cytokines
Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 240 - 247.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
N. Chiang, C. N. Serhan, S.-E. Dahlen, J. M. Drazen, D. W. P. Hay, G. E. Rovati, T. Shimizu, T. Yokomizo, and C. Brink
The Lipoxin Receptor ALX: Potent Ligand-Specific and Stereoselective Actions in Vivo
Pharmacol. Rev., September 1, 2006; 58(3): 463 - 487.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
Y. Birnbaum, Y. Ye, Y. Lin, S. Y. Freeberg, S. P. Nishi, J. D. Martinez, M.-H. Huang, B. F. Uretsky, and J. R. Perez-Polo
Augmentation of Myocardial Production of 15-Epi-Lipoxin-A4 by Pioglitazone and Atorvastatin in the Rat
Circulation, August 29, 2006; 114(9): 929 - 935.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. Bonnans, K. Fukunaga, M. A. Levy, and B. D. Levy
Lipoxin A4 Regulates Bronchial Epithelial Cell Responses to Acid Injury
Am. J. Pathol., April 1, 2006; 168(4): 1064 - 1072.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Fiorucci, E. Distrutti, A. Mencarelli, G. Rizzo, A. R. D. Lorenzo, M. Baldoni, P. del Soldato, A. Morelli, and J. L. Wallace
Cooperation between Aspirin-Triggered Lipoxin and Nitric Oxide (NO) Mediates Antiadhesive Properties of 2-(Acetyloxy)benzoic Acid 3-(Nitrooxymethyl)phenyl Ester (NCX-4016) (NO-Aspirin) on Neutrophil-Endothelial Cell Adherence
J. Pharmacol. Exp. Ther., June 1, 2004; 309(3): 1174 - 1182.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
B. McMahon and C. Godson
Lipoxins: endogenous regulators of inflammation
Am J Physiol Renal Physiol, February 1, 2004; 286(2): F189 - F201.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. Sharon, I. Bar-Joseph, G. E. Mirick, C. N. Serhan, and D. J. Selkoe
Altered Fatty Acid Composition of Dopaminergic Neurons Expressing {alpha}-Synuclein and Human Brains with {alpha}-Synucleinopathies
J. Biol. Chem., December 12, 2003; 278(50): 49874 - 49881.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
M. Sjostrom, A.-S. Johansson, O. Schroder, H. Qiu, J. Palmblad, and J. Z. Haeggstrom
Dominant Expression of the CysLT2 Receptor Accounts for Calcium Signaling by Cysteinyl Leukotrienes in Human Umbilical Vein Endothelial Cells
Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): e37 - 41.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
F. N. E. Gavins, S. Yona, A. M. Kamal, R. J. Flower, and M. Perretti
Leukocyte antiadhesive actions of annexin 1: ALXR- and FPR-related anti-inflammatory mechanisms
Blood, May 15, 2003; 101(10): 4140 - 4147.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
T. Kucharzik, A. T. Gewirtz, D. Merlin, J. L. Madara, and I. R. Williams
Lateral membrane LXA4 receptors mediate LXA4's anti-inflammatory actions on intestinal epithelium
Am J Physiol Cell Physiol, April 1, 2003; 284(4): C888 - C896.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
C. Brink, S.-E. Dahlen, J. Drazen, J. F. Evans, D. W. P. Hay, S. Nicosia, C. N. Serhan, T. Shimizu, and T. Yokomizo
International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors
Pharmacol. Rev., March 1, 2003; 55(1): 195 - 227.
[Abstract] [Full Text] [PDF]

Home page
 J. Dent. Res.Home page
T. E. Van Dyke and C.N. Serhan
Resolution of Inflammation: A New Paradigm for the Pathogenesis of Periodontal Diseases
J. Dent. Res., February 1, 2003; 82(2): 82 - 90.
[Abstract] [Full Text] [PDF]

Home page
 Crit. Rev. Oral Biol. Med.Home page
A. Kantarci and T. E. Van Dyke
LIPOXINSIN CHRONIC INFLAMMATION
Crit. Rev. Oral. Biol. Med., January 1, 2003; 14(1): 4 - 12.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
A. J. Schottelius, C. Giesen, K. Asadullah, I. M. Fierro, S. P. Colgan, J. Bauman, W. Guilford, H. D. Perez, and J. F. Parkinson
An Aspirin-Triggered Lipoxin A4 Stable Analog Displays a Unique Topical Anti-Inflammatory Profile
J. Immunol., December 15, 2002; 169(12): 7063 - 7070.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
I. M. Fierro, J. L. Kutok, and C. N. Serhan
Novel Lipid Mediator Regulators of Endothelial Cell Proliferation and Migration: Aspirin-Triggered-15R-Lipoxin A4 and Lipoxin A4
J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 385 - 392.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Hui, G. Yang, H. Galczenski, D. J. Figueroa, C. P. Austin, N. G. Copeland, D. J. Gilbert, N. A. Jenkins, and C. D. Funk
The Murine Cysteinyl Leukotriene 2 (CysLT2) Receptor. cDNA AND GENOMIC CLONING, ALTERNATIVE SPLICING, AND IN VITRO CHARACTERIZATION
J. Biol. Chem., December 7, 2001; 276(50): 47489 - 47495.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
C. D. Funk
Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology
Science, November 30, 2001; 294(5548): 1871 - 1875.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the American Society for Investigative Pathology.