期刊
BLOOD
卷 112, 期 3, 页码 848-855出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-11-122598
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资金
- NIAMS NIH HHS [P30 AR42689, P30 AR042689] Funding Source: Medline
- NIDCR NIH HHS [P50 DE016191, P50-DE016191] Funding Source: Medline
- NIDDK NIH HHS [DK074448, R01 DK074448] Funding Source: Medline
- NIGMS NIH HHS [GM38765, R01 GM038765, R37 GM038765] Funding Source: Medline
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, RvEi 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 (similar to 40%) in venules of mice. In human platelet-rich plasma (PRP), RvEi selectively blocked both ADP-stimulated and thromboxane receptor agonist U46619-stimulated platelet aggregation in a concentrationdependent manner. In contrast, Delta 6,14-trans-RvEi 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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