Transmigration and activation of neutrophils in the lung reflect key steps in the progression of acute lung injury (ALI). It is known that hydrogen sulfide (H2S) can limit neutrophil activation, but the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. In vivo, C57BL/6N mice received the H2S slow releasing compound GYY4137 prior to lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury, inflammation, and neutrophil transmigration that were inhibited in response to H2S pretreatment. Moreover, H2S reduced mRNA expression of macrophage inflammatory protein-2 (MIP-2) and its receptor in lung tissue, as well as the accumulation of MIP-2 and interleukin-1β in the alveolar space. In vitro, GYY4137 did not exert toxic effects on Hoxb8 neutrophils, but prevented their transmigration through an endothelial barrier in the presence and absence of MIP-2. In addition, the release of MIP-2 and reactive oxygen species from LPS-stimulated Hoxb8 neutrophils were directly inhibited by H2S. Taken together, we provide first evidence that H2S limits lung neutrophil sequestration upon LPS challenge. As proposed underlying mechanisms, H2S prevents neutrophil transmigration through the inflamed endothelium and directly inhibits pro-inflammatory as well as oxidative signalling in neutrophils. Subsequently, H2S pretreatment ameliorates LPS-induced ALI.
We present a new approach to regulating traffic related pollution in urban environments by utilising hybrid vehicles. We give a number of different strategies and some variants of how to achieve this. The efficacy of our approach is exemplified both by the construction of a proof of concept vehicle and by extensive simulations.
Parking spaces are resources that can be pooled together and shared, especially when there are complementary day-time and night-time users. We answer two design questions. First, given a quality of service requirement, how many spaces should be set aside as contingency during day-time for night-time users? Next, how can we replace the first-come-first-served access method by one that aims at optimal efficiency while keeping user preferences private?
Co-registration of SPECT and diagnostic CT using a cost-effective immobilisation device provides excellent accuracy for tumour detection of endocrine malignancies and is superior to SPECT and CT alone. Image fusion reduces false positive results and can detect additional lesions. Anatomical information provided by CT enables precise localisation of abnormalities observed in SPECT.
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