Local Suppression of T Cell Responses by Arginase-Induced L-Arginine Depletion in Nonhealing Leishmaniasis

The balance between T helper (Th) 1 and Th2 cell responses is a major determinant of the outcome of experimental leishmaniasis, but polarized Th1 or Th2 responses are not sufficient to account for healing or nonhealing. Here we show that high arginase activity, a hallmark of nonhealing disease, is primarily expressed locally at the site of pathology. The high arginase activity causes local depletion of L-arginine, which impairs the capacity of T cells in the lesion to proliferate and to produce interferon-γ, while T cells in the local draining lymph nodes respond normally. Healing, induced by chemotherapy, resulted in control of arginase activity and reversal of local immunosuppression. Moreover, competitive inhibition of arginase as well as supplementation with L-arginine restored T cell effector functions and reduced pathology and parasite growth at the site of lesions. These results demonstrate that in nonhealing leishmaniasis, arginase-induced L-arginine depletion results in impaired T cell responses. Our results identify a novel mechanism in leishmaniasis that contributes to the failure to heal persistent lesions and suggest new approaches to therapy

The effect of water on methane oxidation over Pd/Al2O3 under lean, stoichiometric and rich conditions

In this study, the effect of oxygen concentration and the presence of water on methane oxidation were examined over a Pd/Al2O3 catalyst. The physicochemical properties of the catalyst were investigated in detail using BET, XRD, STEM, O-2-TPO and CH4-TPR. Ramping experiments from 150 to 700 degrees C were conducted using rich, stoichiometric and lean gas mixtures in the absence and presence of water. It was found that increasing the oxygen concentration in a dry atmosphere resulted in higher methane oxidation activity, which can be connected to the facilitation of palladium oxide formation. The TPO data showed that only minor amounts of PdO up to 700 degrees C were decomposed; however, in the stoichiometric and rich reaction mixture, PdO was still decomposed because of the oxygen limitation. This fact resulted in a "negative activation" during cooling, with increased activity because of palladium re-oxidation. Moreover, methane steam reforming and water gas shift reactions were important reactions under rich conditions over the metallic palladium sites. A significant inhibiting effect of water on the Pd-catalyst with loss of methane activity was found. Interestingly, the inhibition effect was much greater using high oxygen concentration in the gas mixture (500 ppm CH4, 8% O-2, 5% H2O) than that at lower oxygen levels (800-1200 ppm) and we propose that the hydroxyl species formation, which blocks the active sites, are facilitated by a large oxygen excess. In addition, the re-oxidation of palladium occurring during the cooling ramp in dry feed using rich and stoichiometric gas mixtures was also significantly suppressed in the presence of a large amount of water. Thus, water impedes the oxidation of palladium, which significantly deactivates the Pd catalyst

The influence of gas composition on Pd-based catalyst activity in methane oxidation - inhibition and promotion by NO

The individual influence, as well as the combined effect of H2O and NO on the activity of Pd/Al2O3, PtPd/Al2O3 and PtPd/CeAl2O3 catalysts in complete methane oxidation under lean conditions were investigated. Under temperature-programmed ramping experiments the activity was severely inhibited in the presence of 5 vol.% H2O in the reaction mixture. We propose that this is due to blocking by both water and hydroxyl species. Under the influence of NO without water in the gas flow, it was found that the methane oxidation activity was partly suppressed, due to blocking of active sites. Indeed TPD performed after ramping experiments showed NOx storage on the catalyst. Contrary to the negative effect of NO in the dry case, the promotional NO effect on the activity was observed when water was co-fed, comparing the case with only water presence. The promotional NO effect was confirmed with isothermal experiments, where e.g. the methane conversion decreased from initial 96% to 25% after 10 h of exposure in CH4-O-2-H2O mixture at 450 degrees C over the Pd/Al2O3 sample, while the decrease was only from 88% to 60% when catalyst was exposed to CH4-O-2-H2O-NO mixture. We propose that the reason is that the NO reacts with the hydroxyl species to form HNO2, which reduces the water deactivation effect

An Experimental and Kinetic Modelling Study for Methane Oxidation over Pd-based Catalyst: Inhibition by Water

The water inhibition of methane oxidation over a bimetallic Pt-Pd on CeO2-Al2O3 catalyst was investigated and the experimental data were used to develop a kinetic model, consisting of only three reaction steps. In the model, the water effect was assigned to the adsorption of H2O on surface sites, as well as to the formation and accumulation of surface hydroxyl groups. These two effects were accounted by the model, which could well describe the experimental data obtained under various conditions