Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen-induced pulmonary inflammation in mice.

BACKGROUND: Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil migration in a CB2 receptor/Gi/o -dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2-AG into eicosanoids. Here, we explored the direct contribution of specific CB2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo. METHODS: In vitro studies including CB2 expression, adhesion and migratory responsiveness, respiratory burst, degranulation, and calcium mobilization were conducted in human peripheral blood eosinophils and mouse bone marrow-derived eosinophils. Allergic airway inflammation was assessed in mouse models of acute OVA-induced asthma and directed eosinophil migration. RESULTS: CB2 expression was significantly higher in eosinophils from symptomatic allergic donors. The selective CB2 receptor agonist JWH-133 induced a moderate migratory response in eosinophils. However, short-term exposure to JWH-133 potently enhanced chemoattractant-induced eosinophil shape change, chemotaxis, CD11b surface expression, and adhesion as well as production of reactive oxygen species. Receptor specificity of the observed effects was confirmed in eosinophils from CB2 knockout mice and by using the selective CB2 antagonist SR144528. Of note, systemic application of JWH-133 clearly primed eosinophil-directed migration in vivo and aggravated both AHR and eosinophil influx into the airways in a CB2 -specific manner. This effect was completely absent in eosinophil-deficient ∆dblGATA mice. CONCLUSION: Our data indicate that CB2 may directly contribute to the pathogenesis of eosinophil-driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB2 -mediated priming of eosinophils. Hence, antagonism of CB2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.

Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial.

BACKGROUND: Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in southeast Asia. Although no treatment is currently available, vaccination effectively prevents the disease. In a non-inferiority study, we aimed to compare the safety and immunogenicity of a novel, second-generation, inactivated candidate vaccine for JEV with a licensed, mouse-brain-derived vaccine. METHODS: We included 867 adults in a multicentre, multinational, observer-blinded, randomised controlled phase III trial. Study sites were located in the USA, Germany, and Austria. Volunteers received either the JEV test vaccine intramuscularly on a two-dose schedule (on days 0 and 28; n=430) or the licensed vaccine subcutaneously according to its recommended three-dose schedule (on days 0, 7, and 28; n=437). The primary endpoint was immunogenicity, with respect to neutralising JEV-specific antibodies assessed by a plaque-reduction neutralisation test, which was assessable in 725 patients in the per-protocol population. This trial is registered as a clinical trial, EudraCT number 2004-002474-36. FINDINGS: The safety profile of the test vaccine was good, and its local tolerability profile was more favourable than that of the licensed vaccine. Frequency of adverse events was similar between treatment groups, and vaccine-related adverse events were generally mild. The seroconversion rate of the test vaccine was 98% compared with 95% for the licensed vaccine on day 56 (95% CI for the difference -1.33 to 3.43). Geometric mean titre for recipients of the test vaccine was 244 (range 5-19 783), compared with 102 (5-1864) for the licensed vaccine (ratio 2.3 [95% CI 1.967-2.75]). INTERPRETATION: The test JEV vaccine has a promising immunogenicity and safety profile.

Mass effects of quartz resonant sensors with different surface microstructures in liquids.

Liquid trapped by the rough surface of a quartz resonator vibrating in thickness-shear mode (TSM) will act as a mass effect to the crystal. It has been proven that this mass effect not only depends on the liquid mass enclosed in the surface cavities, but also the liquid properties and the crystal surface features. Based on a series of experiments, this paper introduces "trapping factor" to analyze the mechanism of the liquid mass effect. Influences of different surface microstructures, including structure dimension and orientation, on the liquid mass effect have been studied on 10 MHz fundamental mode AT-cut resonators. The result indicates that the trapping factor of a chess-board structure has no advantage compared to a line-structure. For the same structure height of 0.4 microm, the mass effect of a crystal with about 3 microm distance line-structure is bigger than that of a 7.5 microm distance line-structure. With a similar surface roughness value (R (a)), the crystal with a line structured surface has a much bigger mass effect than that with a randomly rough surface.