| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
Resolvin E1 (RvE1) is a potent anti-inflammatory and proresolving mediator derived from omega-3 eicosapentaenoic acid generated during the resolution phase of inflammation. RvE1 possesses a unique structure and counterregulatory actions that stop human polymorphonuclear leukocyte (PMN) transendothelial migration and PMN infiltration in several murine inflammatory models. To examine the mechanism(s) underlying anti-inflammatory actions on PMNs, we prepared [3H]RvE1 and characterized its interactions with human PMN. Results with membrane fractions of human PMN demonstrated specific binding with a Kd of 48.3 nM. [3H]RvE1 specific binding to human PMN was displaced by leukotriene B4 (LTB4) and LTB4 receptor 1 (BLT1) antagonist U-75302, but not by chemerin peptide, a ligand specific for another RvE1 receptor ChemR23. Recombinant human BLT1 gave specific binding with [3H]RvE1 with a Kd of 45 nM. RvE1 selectively inhibited adenylate cyclase with BLT1, but not with BLT2. In human PBMC, RvE1 partially induced calcium mobilization, and blocked subsequent stimulation by LTB4. RvE1 also attenuated LTB4-induced NF-
B activation in BLT1-transfected cells. In vivo anti-inflammatory actions of RvE1 were sharply reduced in BLT1 knockout mice when given at low doses (100 ng i.v.) in peritonitis. In contrast, RvE1 at higher doses (1.0 µg i.v.) significantly reduced PMN infiltration in a BLT1-independent manner. These results indicate that RvE1 binds to BLT1 as a partial agonist, potentially serving as a local damper of BLT1 signals on leukocytes along with other receptors (e.g., ChemR23-mediated counterregulatory actions) to mediate the resolution of inflammation.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This study was supported, in part, by National Institutes of Health Grants GM38765, DK074448, and P50-DE016191 (to C.N.S.).
2 Current address: Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, Japan.
3 Address correspondence and reprint requests to Dr. Charles N. Serhan, Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115. E-mail address: cnserhan{at}zeus.bwh.harvard.edu
4 Abbreviations used in this paper: Rv, resolvin; EPA, eicosapentaenoic acid; PMN, polymorphonuclear leukocyte; RvE1, resolvin E1; 5-LO, 5-lipoxygenase; GPCR, G protein-coupled receptors; LTB4, leukotriene B4; PTX, pertussis toxin; WT, wild type; CHO, Chinese hamster ovary; BLT1, LTB4 receptor 1; BLT2, LTB4 receptor type 2; DC, dendritic cell; ALX, LXA4 receptor.
This article has been cited by other articles:
|
|
 |
|
  M. Dona, G. Fredman, J. M. Schwab, N. Chiang, M. Arita, A. Goodarzi, G. Cheng, U. H. von Andrian, and C. N. Serhan Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets Blood, August 1, 2008; 112(3): 848 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Gubitosi-Klug, R. Talahalli, Y. Du, J. L. Nadler, and T. S. Kern 5-Lipoxygenase, but Not 12/15-Lipoxygenase, Contributes to Degeneration of Retinal Capillaries in a Mouse Model of Diabetic Retinopathy Diabetes, May 1, 2008; 57(5): 1387 - 1393. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Cash, R. Hart, A. Russ, J. P.C. Dixon, W. H. Colledge, J. Doran, A. G. Hendrick, M. B.L. Carlton, and D. R. Greaves Synthetic chemerin-derived peptides suppress inflammation through ChemR23 J. Exp. Med., April 14, 2008; 205(4): 767 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hasturk, A. Kantarci, E. Goguet-Surmenian, A. Blackwood, C. Andry, C. N. Serhan, and T. E. Van Dyke Resolvin E1 Regulates Inflammation at the Cellular and Tissue Level and Restores Tissue Homeostasis In Vivo J. Immunol., November 15, 2007; 179(10): 7021 - 7029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Haworth and B. D. Levy Endogenous lipid mediators in the resolution of airway inflammation Eur. Respir. J., November 1, 2007; 30(5): 980 - 992. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
