Neutrophils play a critical role in acute and chronic inflammatory processes, including myocardial ischemia/reperfusion injury, sepsis, and adult respiratory distress syndrome. Binding of formyl peptide receptor 1 (FPR1) by N-formyl peptides can activate neutrophils and may represent a new therapeutic target in either sterile or septic inflammation. Propofol, a widely used i.v. anesthetic, has been shown to modulate immunoinflammatory responses. However, the mechanism of propofol remains to be established. In this study, we showed that propofol significantly reduced superoxide generation, elastase release, and chemotaxis in human neutrophils activated by fMLF. Propofol did not alter superoxide generation or elastase release in a cell-free system. Neither inhibitors of γ-aminobutyric acid receptors nor an inhibitor of protein kinase A reversed the inhibitory effects of propofol. In addition, propofol showed less inhibitory effects in non-FPR1–induced cell responses. The signaling pathways downstream from FPR1, involving calcium, AKT, and ERK1/2, were also competitively inhibited by propofol. These results show that propofol selectively and competitively inhibits the FPR1-induced human neutrophil activation. Consistent with the hypothesis, propofol inhibited the binding of N-formyl-Nle-Leu-Phe-Nle-Tyr-Lys-fluorescein, a fluorescent analog of fMLF, to FPR1 in human neutrophils, differentiated THP-1 cells, and FPR1-transfected human embryonic kidney-293 cells. To our knowledge, our results identify, for the first time, a novel anti-inflammatory mechanism of propofol by competitively blocking FPR1 in human neutrophils. Considering the importance of N-formyl peptides in inflammatory processes, our data indicate that propofol may have therapeutic potential to attenuate neutrophil-mediated inflammatory diseases by blocking FPR1.
Novel designs of a cylindrical and a flat portable direct methanol fuel cell (DMFC) have been proposed in this research. Experimental cells have also been fabricated. Their maximum power output reached 12mW∕cm2 when operating at room temperature and with naturally breathed air. The weight and the volume of the experimental cylindrical cell are 27g and 30cm3, respectively, with 7.5cm3 of methanol inside. Its specific power and volumetric power density are 6.67mW∕g and 6.25mW∕cm3, respectively. The membrane electrode assembly was fabricated by hot pressing the electrodes purchased from E-Tek Co. The catalyst contents are 4.0mg∕cm2 of Pt∕Ru (80wt.% carbon supported) and 4.0mg∕cm2 of Pt (black) for anode and cathode, respectively. The new and compact design will make the portable DMFC lighter and cheaper, and bring it one step closer to be marketable.
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