Resolvin E1, an EPA-derived mediator in whole blood, selectively counterregulates leukocytes and platelets. Blood

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, USA.
Blood (Impact Factor: 10.45). 06/2008; 112(3):848-55. DOI: 10.1182/blood-2007-11-122598
Source: PubMed


Resolvin E1 (RvE1) is an omega-3 eicosapentaenoic acid (EPA)-derived lipid mediator generated during resolution of inflammation and in human vasculature via leukocyte-endothelial cell interactions. RvE1 possesses anti-inflammatory and proresolving actions. Here, we report that RvE1 in human whole blood rapidly regulates leukocyte expression of adhesion molecules. RvE1 in the 10- to 100-nM range stimulated L-selectin shedding, while reducing CD18 expression in both neutrophils and monocytes. When added to whole blood, RvE1 did not stimulate reactive oxygen species by either neutrophils or monocytes, nor did it directly stimulate cytokine/chemokine production in heparinized blood. Intravital microscopy (IVM) demonstrated that RvE1 rapidly reduced leukocyte rolling (approximately 40%) in venules of mice. In human platelet-rich plasma (PRP), RvE1 selectively blocked both ADP-stimulated and thromboxane receptor agonist U46619-stimulated platelet aggregation in a concentration-dependent manner. In contrast, Delta 6,14-trans-RvE1 isomer was inactive. RvE1 did not block collagen-stimulated aggregation, and regulation of ADP-induced platelet aggregation was not further enhanced with aspirin treatment. These results indicate RvE1 is a potent modulator of leukocytes as well as selective platelet responses in blood and PRP, respectively. Moreover, the results demonstrate novel agonist-specific antiplatelet actions of RvE1 that are potent and may underlie some of the beneficial actions of EPA in humans.

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Available from: Jan M Schwab, Feb 28, 2014
    • "RvE1 was readily shown to decrease PMN infiltration and T cell migration, to reduce TNFα and IFNγ secretion, to inhibit chemokine formation and to block IL-1-induced NF-κB activation (Bannenberg and Serhan, 2010; Schwab et al., 2007). RvE1 was also shown to stimulate macrophage phagocytosis of apoptotic PMN and to be a potent counter-regulator of L-selectin expression (Schwab et al., 2007; Dona et al., 2008). RvE1 displayed potent anti-inflammatory actions in vivo, protecting mice against experimental periodontitis, colitis, peritonitis and brain ischemia–reperfusion (Arita et al., 2005; Bannenberg and Serhan, 2010). "
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    ABSTRACT: A novel genus of pro-resolving lipid mediators endogenously generated from omega-3 polyunsaturated fatty acids has been identified in exudates obtained during the resolution phase of acute inflammation. The term specialized pro-resolving mediators (SPM) has been coined for these lipid mediators, comprising four novel chemical mediator families designated resolvins of the E series (if derived from eicosapentaenoic acid) and resolvins of the D series, protectins and maresins (if generated from docosahexaenoic acid). These SPM act not only as "stop-signals" of inflammatory response, but also as facilitators of the ability of macrophages to clear apoptotic cells (efferocytosis) and migrate to peripheral lymph nodes (efflux), thus, expediting their removal from sites of inflammation. In this review, we provide an overview of the current efforts to elucidate the structure-function, biosynthesis and actions of these omega-3-derived SPM in the context of inflammatory diseases. We specifically highlight the role of these SPM as endogenous counter-regulators of the persistent inflammatory status present in adipose tissue of obese individuals and describe the potential therapeutic impact of these bioactive lipid autacoids on the prevention of hepatic co-morbidities associated with obesity and the metabolic syndrome. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 05/2015; DOI:10.1016/j.ejphar.2015.03.092 · 2.53 Impact Factor
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    • "ALA treatment groups were received either pure ALA or its mixture with linoleic acid (ALA: linoleic acid = 1:1) at 50, 100, or 250 mg/kg for 10 days. Following the last administration, platelet-rich plasma (PRP) was prepared and obtained from blood samples according to the previous methods [16, 17]. Brifely, the sample containing 3.8% sodium citrate were centrifuged at 100 × g for 10 min at room temperature to obtain the PRP in supernatant. "
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    ABSTRACT: Background The current study was to evaluate the anti-thrombotic effect of alpha-linolenic acid (ALA) which was isolated and purified from Jiaomu in vivo. Methods The seeds were crushed and subsequently subjected to saponification, acid hydrolysis, gradient freezing, urea inclusion and complexation of silver nitrate to obtain the unsaturated fatty acids. The chemical characteristics of isolated ALA were validated by 1HNMR, 13CNMR and mass spectrometry, and then the anti-thrombotic effect of ALA and its mixture with linoleic acid (1:1) were evaluated in the following experiments. Results The alpha-linolenic acid was isolated and purified from Jiaomu through our newly established methods. ALA and its mixture with linoleic acid can prolong the hemorrhage and coagulation time as well as enhanced the survival rate of mice subjected to collagen-adrenaline induced thrombosis. In addition, the thrombosis on A-V bypass and platelet aggregation of rats will be reduced after treated with ALA or its mixture, and the expression level of Akt and PI3K protein decreased 26% and 31%, respectively. Conclusions We designed and optimized a very simple and high-yield procedure to isolate ALA and linoleic acid mixture from seeds of Zanthoxylum bungeanum Maxim and demonstrated that such mixture can obtain a good anti-thrombotic effect through the modulation of PI3K/Akt signaling.
    BMC Complementary and Alternative Medicine 09/2014; 14(1):348. DOI:10.1186/1472-6882-14-348 · 2.02 Impact Factor
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    • "In all aggregation tests, it appeared that, in contrast to E,Z,E derivatives, the non E,Z,E ones tested (E,E,Z and E,E,E) are devoid of inhibitory effect [20]. This is in agreement with a previous paper reporting that PD1 (E,E,Z motif) is a weak inhibitor of ADPinduced platelet aggregation [23]. Very recent data, obtained in a completely different biological system, have shown that PDX, but not PD1, can improve insulin sensitivity in skeletal muscle of obese diabetic mice [24]. "
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    ABSTRACT: More and more attention is paid to omega-3 fatty acids because of their potential activities in preventing cardiovascular events. In this brief review, we focus on the lipoxygenase end-metabolites of two relevant nutrients belonging to the omega-3 family fatty acids: alpha-linolenic and docosahexaenoic acids, the latter being a prominent component of brain lipids. Dihydroxylated derivatives are described as well as their inhibitory effects on platelet aggregation and cyclooxygenase activities. We point out that only the dihydroxylated products with the trans,cis,trans/E,Z,E conjugated triene geometry exhibit those inhibitory activities. These properties being found with other polyunsaturated fatty acid oxygenated products sharing the same E,Z,E molecular motif, they have been collectively named poxytrins. From alpha-linolenic and docosahexaenoic acids, poxytrins are linotrins and protectin DX, respectively.
    Biochimie 09/2014; 107. DOI:10.1016/j.biochi.2014.09.008 · 2.96 Impact Factor
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