35 research outputs found

    Labile disulfide bonds are common at the leucocyte cell surface

    Get PDF
    Redox conditions change in events such as immune and platelet activation, and during viral infection, but the biochemical consequences are not well characterized. There is evidence that some disulfide bonds in membrane proteins are labile while others that are probably structurally important are not exposed at the protein surface. We have developed a proteomic/mass spectrometry method to screen for and identify non-structural, redox-labile disulfide bonds in leucocyte cell-surface proteins. These labile disulfide bonds are common, with several classes of proteins being identified and around 30 membrane proteins regularly identified under different reducing conditions including using enzymes such as thioredoxin. The proteins identified include integrins, receptors, transporters and cell–cell recognition proteins. In many cases, at least one cysteine residue was identified by mass spectrometry as being modified by the reduction process. In some cases, functional changes are predicted (e.g. in integrins and cytokine receptors) but the scale of molecular changes in membrane proteins observed suggests that widespread effects are likely on many different types of proteins including enzymes, adhesion proteins and transporters. The results imply that membrane protein activity is being modulated by a ‘redox regulator’ mechanism

    The Sphingosine Kinase-Sphingosine-1-Phosphate Axis Is a Determinant of Mast Cell Function and Anaphylaxis

    Get PDF
    SummarySphingosine-1-phosphate, a key mediator in immune cell trafficking, is elevated in the lungs of asthmatic patients and regulates pulmonary epithelium permeability. Stimulation of mast cells by allergens induces two mammalian sphingosine kinases (Sphk1 and Sphk2) to produce sphingosine-1-phosphate (S1P). Little is known about the individual role of these kinases in regulating immune cell function. Here we show that in mast cells, Sphk2 is required for production of S1P, for calcium influx, for activation of protein kinase C, and for cytokine production and degranulation. However, susceptibility to in vivo anaphylaxis is determined both by S1P within the mast cell compartment and by circulating S1P generated by Sphk1 predominantly from a non-mast cell source(s). Thus, sphingosine kinases are determinants of mast cell responsiveness, demonstrating a previously unrecognized relationship with anaphylaxis

    Weed Functional Diversity as Affected by Agroecological Service Crops and No-Till in a Mediterranean Organic Vegetable System

    Get PDF
    This paper explores the effect of agroecological service crops (ASCs), i.e., crops included in the crop rotation for their ecosystem services, terminated with an in-line tillage roller crimper (ILRC) on weed community composition and their functional traits in comparison to a tilled control without ASC. A two-year study was performed in a long-term experiment with vegetables under organic management. Four different cereal crops were introduced as ASCs. Weed abundance and richness and the functional traits were assessed at three different stages, i.e., before and after ASC termination and before harvest of the following crop, melon. All the ASCs showed strong weed suppression, with few differences between the cereals tested. Weed communities with ASCs had later flowering onset and wider flowering span compared to the control, which positively affects weed dispersal and attraction of beneficial insects. However, weed communities with ASCs had higher values for traits related to competition (specific leaf area, seed weight and more perennials). A trade-off between weed suppression and selection of more competitive weed communities by the introduction of ASCs managed with the ILRC should be evaluated in the long-run. The use of the ILRC alternating with other soil management practices seems the more effective strategy to benefit from the minimal soil tillage while avoiding the selection of disservice-related traits in the weed community

    MHC class II-restricted presentation of the major house dust mite allergen Der p 1 Is GILT-dependent: implications for allergic asthma.

    Get PDF
    Gamma-interferon-inducible lysosomal thiol reductase (GILT) is known to reduce disulfide bonds present in proteins internalized by antigen presenting cells, facilitating optimal processing and presentation of peptides on Major Histocompatibility Complex class II molecules, as well as the subsequent activation of CD4-positive T lymphocytes. Here, we show that GILT is required for class II-restricted processing and presentation of immunodominant epitopes from the major house dust mite allergen Der p 1. In the absence of GILT, CD4-positive T cell responses to Der p 1 are significantly reduced, resulting in mitigated allergic airway inflammation in response to Der p 1 and house dust mite extracts in a murine model of asthma
    corecore