100 research outputs found
Activation of the innate immune receptor Dectin-1 upon formation of a 'phagocytic synapse'.
Innate immune cells must be able to distinguish between direct binding to microbes and detection of components shed from the surface of microbes located at a distance. Dectin-1 (also known as CLEC7A) is a pattern-recognition receptor expressed by myeloid phagocytes (macrophages, dendritic cells and neutrophils) that detects β-glucans in fungal cell walls and triggers direct cellular antimicrobial activity, including phagocytosis and production of reactive oxygen species (ROS). In contrast to inflammatory responses stimulated upon detection of soluble ligands by other pattern-recognition receptors, such as Toll-like receptors (TLRs), these responses are only useful when a cell comes into direct contact with a microbe and must not be spuriously activated by soluble stimuli. In this study we show that, despite its ability to bind both soluble and particulate β-glucan polymers, Dectin-1 signalling is only activated by particulate β-glucans, which cluster the receptor in synapse-like structures from which regulatory tyrosine phosphatases CD45 and CD148 (also known as PTPRC and PTPRJ, respectively) are excluded (Supplementary Fig. 1). The 'phagocytic synapse' now provides a model mechanism by which innate immune receptors can distinguish direct microbial contact from detection of microbes at a distance, thereby initiating direct cellular antimicrobial responses only when they are required
Immunomodulatory Activity of Dietary Fiber: Arabinoxylan and Mixed-Linked Beta-Glucan Isolated from Barley Show Modest Activities in Vitro
High intake of dietary fiber is claimed to protect against development of colorectal cancer. Barley is a rich source of dietary fiber, and possible immunomodulatory effects of barley polysaccharides might explain a potential protective effect. Dietary fiber was isolated by extraction and enzyme treatment. A mixed-linked β-glucan (WSM-TPX, 96.5% β-glucan, Mw 886 kDa), an arabinoxylan (WUM-BS-LA, 96.4% arabinoxylan, Mw 156 kDa), a mixed-linked β-glucan rich fraction containing 10% arabinoxylan (WSM-TP) and an arabinoxylan rich fraction containing 30% mixed-linked β-glucan (WUM-BS) showed no significant effect on IL-8 secretion and proliferation of two intestinal epithelial cell lines, Caco-2 and HT-29, and had no significant effect on the NF-κB activity in the monocytic cell line U937-3κB-LUC. Further enriched arabinoxylan fractions (WUM-BS-LA) from different barley varieties (Tyra, NK96300, SB94897 and CDCGainer) were less active than the mixed-linked β-glucan rich fractions (WSM-TP and WSM-TPX) in the complement-fixing test. The mixed-linked β-glucan rich fraction from NK96300 and CDCGainer showed similar activities as the positive control while mixed-linked β-glucan rich fractions from Tyra and SB94897 were less active. From these results it is concluded that the isolated high molecular weight mixed-linked β-glucans and arabinoxylans from barley show low immunological responses in selected in vitro test systems and thus possible anti-colon cancer effects of barley dietary fiber cannot be explained by our observations
Candida soluble cell wall β-glucan facilitates ovalbumin-induced allergic airway inflammation in mice: Possible role of antigen-presenting cells
<p>Abstract</p> <p>Background</p> <p>Although fungi have been implicated as initiating/deteriorating factors for allergic asthma, their contributing components have not been fully elucidated. We previously isolated soluble β-glucan from <it>Candida albicans </it>(CSBG) (Ohno et al., 2007). In the present study, the effects of CSBG exposure on airway immunopathology in the presence or absence of other immunogenic allergen was investigated <it>in vivo</it>, and their cellular mechanisms were analyzed both <it>in vivo </it>and <it>in vitro</it>.</p> <p>Methods</p> <p><it>In vivo</it>, ICR mice were divided into 4 experimental groups: vehicle, CSBG (25 μg/animal), ovalbumin (OVA: 2 μg/animal), and CSBG + OVA were repeatedly administered intratracheally. The bronchoalveolar lavage cellular profile, lung histology, levels of cytokines and chemokines in the lung homogenates, the expression pattern of antigen-presenting cell (APC)-related molecules in the lung digests, and serum immunoglobulin values were studied. <it>In vitro</it>, the impacts of CSBG (0–12.5 μg/ml) on the phenotype and function of immune cells such as splenocytes and bone marrow-derived dendritic cells (BMDCs) were evaluated in terms of cell proliferation, the surface expression of APC-related molecules, and OVA-mediated T-cell proliferating activity.</p> <p>Results</p> <p><it>In vivo</it>, repeated pulmonary exposure to CSBG induced neutrophilic airway inflammation in the absence of OVA, and markedly exacerbated OVA-related eosinophilic airway inflammation with mucus metaplasia in mice, which was concomitant with the amplified lung expression of Th2 cytokines and IL-17A and chemokines related to allergic response. Exposure to CSBG plus OVA increased the number of cells bearing MHC class II with or without CD80 in the lung compared to that of others. <it>In vitro</it>, CSBG significantly augmented splenocyte proliferation in the presence or absence of OVA. Further, CSBG increased the expression of APC-related molecules such as CD80, CD86, and DEC205 on BMDCs and amplified OVA-mediated T-cell proliferation through BMDCs.</p> <p>Conclusion</p> <p>CSBG potentiates allergic airway inflammation with maladaptive Th immunity, and this potentiation was associated with the enhanced activation of APCs including DC.</p
Virulence of Group A Streptococci Is Enhanced by Human Complement Inhibitors
Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail complement C3 (a critical opsonin) deposition. This results in diminished activation of phagocytes and clearance of GAS that may lead to the host being unable to limit the infection. Herein we describe the course of GAS infection in three human complement inhibitor transgenic (tg) mouse models that examined each inhibitor (human C4BP or FH) alone, or the two inhibitors together (C4BPxFH or 'double' tg). GAS infection with strains that bound C4BP and FH resulted in enhanced mortality in each of the three transgenic mouse models compared to infection in wild type mice. In addition, GAS manifested increased virulence in C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory cytokines and they died earlier than single transgenic or wt controls. The effects of hu-C4BP and hu-FH were specific for GAS strains that bound these inhibitors because strains that did not bind the inhibitors showed reduced virulence in the 'double' tg mice compared to strains that did bind; mortality was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our findings emphasize the importance of binding of complement inhibitors to GAS that results in impaired opsonization and phagocytic killing, which translates to enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg model may prove invaluable in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy
Metallic modified (bismuth, antimony, tin and combinations thereof) film carbon electrodes.
In this paper in situ bismuth, antimony, tin modified electrodes and combinations thereof are explored towards the model target analytes cadmium(II) and lead(II), chosen since they are the most widely studied, to explore the role of the underlying electrode substrate with respect to boron-doped diamond, glassy carbon, and screen-printed graphite electrodes. It is found that differing electrochemical responses are observed, dependent upon the underlying electrode substrate. The electrochemical response using the available range of metallic modifications is only ever observed when the underlying electrode substrate exhibits relatively slow electron transfer properties; in the case of fast electron transfer properties, no significant advantages are evident. Furthermore these bismuth modified systems which commonly employ a pH 4 acetate buffer, reported to ensure the bismuth(III) stability upon the electrode surface can create create a problem when sensing at low concentrations of heavy metals due to its high background current. It is demonstrated that a simple change of pH can allow the detection of the target analytes (cadmium(II) and lead(II)) at levels below that set by the World Health Organisation (WHO) using bare graphite screen-printed electrodes
Determination of the fuel properties of selected packaging waste from the municipal sector
Tworzywo sztuczne jest bardzo popularnym i niedrogim w pozyskaniu materiałem, z tego względu jest powszechnie wykorzystywane w różnych dziedzinach życia. W Europie największym obszarem zastosowań tworzyw sztucznych jest sektor opakowań, który odpowiada za 39,4% ogólnego zapotrzebowania na tworzywa sztuczne. Na tej podstawie można stwierdzić, że tworzywo sztuczne coraz częściej zastępuje tradycyjne materiały opakowaniowe takie jak: szkło, metal, drewno czy papier. W 2012 roku ilość wytworzonych odpadów polimerowych w Europie osiągnęła poziom. 25,2 miliona Mg. Wśród odpadów z tworzyw sztucznych dominują odpady opakowaniowe, stanowiące 62,2% wszystkich odpadów tego typu. W artykule przedstawiono podstawowe właściwości paliwowe odpadów polimerowych z sektora opakowaniowego. Badane odpady pochodzą z grupy poliolefin: polipropylen (PP) oraz polietylen (PE), które stanowią jedną z najpopularniejszych i najliczniejszych grup wśród tworzyw sztucznych. W ciągu ostatnich lat obserwuje się systematyczny spadek ilości odpadów polimerowych kierowanych na składowiska. Pomimo różnych działań ciągle jeszcze na składowiska trafia 38,1% odpadów tworzyw sztucznych. Aby realny stał się do osiągnięcia cel w Europie „zero odpadów tworzyw sztucznych na składowiskach do roku 2020”, należy podjąć bardziej zdecydowane działania.Plastic is a very popular material and not expensive to obtain. Therefore, it is widely used in many branches of life. In Europe the largest where plastics are used is a packaging sector, which covers 39,4% of the total demand for plastics. On this basis we may state that the plastic more and more replaces traditional packaging such as: glass, metal, wood or paper. In 2012 the amount of the polymer wastes produced in Europe reached a level of 25,2 M of Mg. Among plastic wastes the most dominant packaging wastes which constitute 62,2% of all the wastes of this type. The article presents basic fuelling properties of polymer wastes from the packaging sector. Tested wastes belong to the polyolefin group: polypropylene (PP) and polyethylene (PE), which constitutes one of the most popular and most numerous groups of plastics. In the last years we observe a gradual decrease of the amount of polymer wastes directed to landfills. In spite of the various actions which are undertaken, still 38,1% of plastic wastes is directed to landfills. In order to obtain a goal to have in Europe “Zero plastics wastes in landfills by 2020” more decisive actions should be made
Management of pigs’ droppings from a selected farm for energetic purposes
Changes that occur in the energy market force to find out new solutions for searching alternative sources to assure energetic safety and self-sufficiency in this sector of economy. Following these criteria, Council of Ministers in 2010 established on a document called „Directions of development of agricultural biogas plants for the period of time 2010-2020. The document assumed that average 1 biogas plant of 1 MW capacity will be built in each commune. According to these assumptions approximately 2 thousands plants with total power of 2 thousands MWe would be created. The estimated theoretical production capacity in Poland of agricultural biogas based on animals dropping (manure and slurry) exceeds 3M m3. The article presents test results of physic-chemical properties of barley straw, corn cob mix and pig’s droppings.Zmiany zachodzące na rynku energii zmuszają do podejmowania nowych rozwiązań, mających na celu poszukiwanie jej źródeł dla zapewnienia bezpieczeństwa energetycznego i samowystarczalności w tej dziedzinie gospodarki. Kierując się tymi kryteriami, Rada Ministrów w 2010 roku przyjęła dokument pt. „Kierunki rozwoju biogazowni rolniczych w Polsce w latach 2010-2020”, w którym założono powstanie średnio jednej biogazowni o mocy 1 MW w każdej gminie. Przyjęte założenie spowodowałoby powstanie około 2 tysięcy obiektów o mocy 2 tysięcy MWe. Potencjał teoretyczny produkcji biogazu rolniczego w Polsce na bazie odchodów zwierzęcych (gnojowica i obornik) oszacowano na ponad 3 mln m3. W artykule przedstawiono wyniki badań fizyczno-chemicznych: słomy jęczmiennej, kiszonki kukurydzy i odchodów trzody chlewnej
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