75 research outputs found

    Alternative activation of human macrophages enhances tissue factor expression and production of extracellular vesicles

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    Macrophages are versatile cells that can be polarized by the tissue environment to fulfill required needs. Proinflammatory polarization is associated with increased tissue degradation and propagation of inflammation whereas alternative polarization within a Th2 cytokine environment is associated with wound healing and angiogenesis. To understand if polarization of macrophages can lead to a procoagulant macrophage subset we polarized human monocyte derived macrophages to a proinflammatory and an alternative activation state. Alternative polarization with interleukin-4 and IL-13 led to a macrophage phenotype characterized by increased tissue factor (TF) production and release and by an increase in extracellular vesicle production. In addition, also TF activity was enhanced in extracellular vesicles of alternatively polarized macrophages. This TF induction was dependent on signal transducer and activator of transcription-6 signaling and poly ADP ribose polymerase activity. In contrast to monocytes, human macrophages did not show increased tissue factor expression upon stimulation with lipopolysaccharide and interferon-γ. Previous polarization to either a proinflammatory or an alternative activation subset does not change the subsequent stimulation of TF. The inability of proinflammatory activated macrophages to respond to lipopolysaccharide and interferon-γ with an increase in TF production seems to be due to an increase in TF promoter methylation and was reversible when treating these macrophages with a demethylation agent. In conclusion, we provide evidence that proinflammatory polarization of macrophages does not lead to enhanced procoagulatory function, whereas alternative polarization of macrophages leads to an increased expression of TF and increased production of TF bearing extracellular vesicles by these cells suggesting a procoagulatory phenotype of alternatively polarized macrophages

    Seven decades of hydrogeomorphological changes in a near‐natural (Sense River) and a hydropower‐regulated (Sarine River) pre‐Alpine river floodplain in Western Switzerland

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    This is the peer reviewed version which has been published in final form at https://doi.org/10.1002/esp.5017 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Hydropower alteration of the natural flow and sediment regime can severely degrade hydromorphology, thereby threatening biodiversity and overall ecosystem processes of rivers and their floodplains. Using sequences of aerial images, we quantified seven decades (1938/1942–2013) of spatiotemporal changes in channel and floodplain morphology, as well as changes in the physical habitats, of three floodplain river reaches of the Swiss pre‐Alps, two hydropower‐regulated and one near‐natural. In the Sarine River floodplain, within the first decades of hydropower impairment, the magnitude and frequency of flood events (Q2, Q10, Q30) decreased substantially. As a result, the area of pioneer floodplain habitats that depend on flood activity and sediment dynamic, such as bare sediments, decreased dramatically by approximately 95%. However, by 2013 vegetated areas had generally increased in comparison to the pre‐regulation period in 1943, indicating general vegetative colonization. Between 1943 and 2013, the active channel underwent essential narrowing (up to 62% width reduction in the residual flow reach) and habitat turnover rates were very low (5% of the total floodplain area changed habitat type five to six times). In contrast, from the 1950s onwards, the near‐natural floodplain of the Sense River experienced recurrent narrowing and widening, and frequent changes between bare and vegetated areas, reflecting the shifting habitat mosaic concept typical for natural floodplains. In the three reaches investigated, we found that the active floodplain width and erosion of vegetated areas were primarily controlled by medium to large floods (Q10, Q30), which combined with reduced time intervals between ordinary floods ≥ Q2 most likely mobilized streambed sediments and limited the ability of vegetation to establish itself on bare gravel bars within the parafluvial zone. These findings can contribute to restoration action plans such as controlled flooding and sediment replenishments in the Sarine and other floodplain rivers of the Alps

    River Channelization

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    Coupled hydraulic modelling supported by remote sensing data

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