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  1. Article ; Online: Disease-specific glycosaminoglycan patterns in the extracellular matrix of human lung and brain.

    Ennemoser, Maria / Pum, Alexandra / Kungl, Andreas

    Carbohydrate research

    2021  Volume 511, Page(s) 108480

    Abstract: A wide variety of diseases throughout the mammalian organism is characterized by abnormal deposition of various components of the extracellular matrix (ECM), including the heterogeneous family of glycosaminoglycans (GAGs), which contribute considerably ... ...

    Abstract A wide variety of diseases throughout the mammalian organism is characterized by abnormal deposition of various components of the extracellular matrix (ECM), including the heterogeneous family of glycosaminoglycans (GAGs), which contribute considerably to the ECM architecture as part of the so-called proteoglycans. The GAG's unique sulfation pattern, derived from highly dynamic and specific modification processes, has a massive impact on critical mediators such as cytokines and growth factors. Due to the strong connection between the specific sulfation pattern and GAG function, slight alterations of this pattern are often associated with enormous changes at the cell as well as at the organ level. This review aims to investigate the connection between modifications of GAG sulfation patterns and the wide range of pathological conditions, mainly focusing on a range of chronic diseases of the central nervous system (CNS) as well as the respiratory tract.
    MeSH term(s) Animals ; Brain/metabolism ; Chondroitin Sulfates/metabolism ; Extracellular Matrix/metabolism ; Glycosaminoglycans/metabolism ; Humans ; Lung ; Mammals/metabolism ; Proteoglycans
    Chemical Substances Glycosaminoglycans ; Proteoglycans ; Chondroitin Sulfates (9007-28-7)
    Language English
    Publishing date 2021-11-17
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1435-7
    ISSN 1873-426X ; 0008-6215
    ISSN (online) 1873-426X
    ISSN 0008-6215
    DOI 10.1016/j.carres.2021.108480
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The Role of Heparan Sulfate in CCL26-Induced Eosinophil Chemotaxis.

    Pum, Alexandra / Ennemoser, Maria / Gerlza, Tanja / Kungl, Andreas J

    International journal of molecular sciences

    2022  Volume 23, Issue 12

    Abstract: Proinflammatory chemokine ligand 26 (CCL26, eotaxin-3) mediates transendothelial cell migration of eosinophils by binding and activating the G-protein-coupled (GPC) chemokine receptor 3 on the surface of eosinophilic cells. Here we have investigated the ... ...

    Abstract Proinflammatory chemokine ligand 26 (CCL26, eotaxin-3) mediates transendothelial cell migration of eosinophils by binding and activating the G-protein-coupled (GPC) chemokine receptor 3 on the surface of eosinophilic cells. Here we have investigated the role of glycosaminoglycans (GAGs) as potential co-receptors in the process of CCL26-induced eosinophil chemotaxis. For this purpose, we have first identified the GAG-binding site of CCL26 by a site-directed mutagenesis approach in the form of an alanine screening. A panel of GAG-binding-deficient mutants has been designed, generated, and analyzed with respect to their binding affinities to heparan sulphate (HS) by isothermal fluorescence titration studies. This showed that basic amino acids in the α-helical part of CCL26 are strongly involved in GAG-binding. In chemotaxis experiments, we found that decreased GAG-binding affinity correlated with decreased chemotactic activity, which indicates an involvement of GAGs in eosinophil migration. This was further proven by the negative impact of heparinase III treatment and, independently, by the incubation of eosinophils with an anti heparan sulfate antibody. We finally investigated eosinophils' proteoglycan (PG) expression patterns by real-time PCR, which revealed the highest expression level for serglycin. Including an anti-serglycin antibody in CCL26-induced eosinophil migration experiments reduced the chemotaxis of these immune cells, thereby proving the dependence of eosinophil mobilization on the proteoglycan serglycin.
    MeSH term(s) Chemokine CCL26 ; Chemokines, CC/metabolism ; Chemotaxis ; Chemotaxis, Leukocyte ; Eosinophils ; Glycosaminoglycans/metabolism ; Heparitin Sulfate/metabolism ; Proteoglycans/metabolism
    Chemical Substances Chemokine CCL26 ; Chemokines, CC ; Glycosaminoglycans ; Proteoglycans ; Heparitin Sulfate (9050-30-0)
    Language English
    Publishing date 2022-06-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23126519
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  3. Article: Disease-specific glycosaminoglycan patterns in the extracellular matrix of human lung and brain

    Ennemoser, Maria / Pum, Alexandra / Kungl, Andreas

    Carbohydrate research. 2022 Jan., v. 511

    2022  

    Abstract: A wide variety of diseases throughout the mammalian organism is characterized by abnormal deposition of various components of the extracellular matrix (ECM), including the heterogeneous family of glycosaminoglycans (GAGs), which contribute considerably ... ...

    Abstract A wide variety of diseases throughout the mammalian organism is characterized by abnormal deposition of various components of the extracellular matrix (ECM), including the heterogeneous family of glycosaminoglycans (GAGs), which contribute considerably to the ECM architecture as part of the so-called proteoglycans. The GAG's unique sulfation pattern, derived from highly dynamic and specific modification processes, has a massive impact on critical mediators such as cytokines and growth factors. Due to the strong connection between the specific sulfation pattern and GAG function, slight alterations of this pattern are often associated with enormous changes at the cell as well as at the organ level. This review aims to investigate the connection between modifications of GAG sulfation patterns and the wide range of pathological conditions, mainly focusing on a range of chronic diseases of the central nervous system (CNS) as well as the respiratory tract.
    Keywords brain ; cytokines ; extracellular matrix ; glycosaminoglycans ; humans ; lungs ; proteoglycans ; research
    Language English
    Dates of publication 2022-01
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1435-7
    ISSN 1873-426X ; 0008-6215
    ISSN (online) 1873-426X
    ISSN 0008-6215
    DOI 10.1016/j.carres.2021.108480
    Database NAL-Catalogue (AGRICOLA)

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  4. Article ; Online: The Role of Heparan Sulfate in CCL26-Induced Eosinophil Chemotaxis

    Alexandra Pum / Maria Ennemoser / Tanja Gerlza / Andreas J. Kungl

    International Journal of Molecular Sciences, Vol 23, Iss 6519, p

    2022  Volume 6519

    Abstract: Proinflammatory chemokine ligand 26 (CCL26, eotaxin-3) mediates transendothelial cell migration of eosinophils by binding and activating the G-protein-coupled (GPC) chemokine receptor 3 on the surface of eosinophilic cells. Here we have investigated the ... ...

    Abstract Proinflammatory chemokine ligand 26 (CCL26, eotaxin-3) mediates transendothelial cell migration of eosinophils by binding and activating the G-protein-coupled (GPC) chemokine receptor 3 on the surface of eosinophilic cells. Here we have investigated the role of glycosaminoglycans (GAGs) as potential co-receptors in the process of CCL26-induced eosinophil chemotaxis. For this purpose, we have first identified the GAG-binding site of CCL26 by a site-directed mutagenesis approach in the form of an alanine screening. A panel of GAG-binding-deficient mutants has been designed, generated, and analyzed with respect to their binding affinities to heparan sulphate (HS) by isothermal fluorescence titration studies. This showed that basic amino acids in the α-helical part of CCL26 are strongly involved in GAG-binding. In chemotaxis experiments, we found that decreased GAG-binding affinity correlated with decreased chemotactic activity, which indicates an involvement of GAGs in eosinophil migration. This was further proven by the negative impact of heparinase III treatment and, independently, by the incubation of eosinophils with an anti heparan sulfate antibody. We finally investigated eosinophils’ proteoglycan (PG) expression patterns by real-time PCR, which revealed the highest expression level for serglycin. Including an anti-serglycin antibody in CCL26-induced eosinophil migration experiments reduced the chemotaxis of these immune cells, thereby proving the dependence of eosinophil mobilization on the proteoglycan serglycin.
    Keywords CCL26 ; eotaxin-3 ; glycosaminoglycans ; GAG ; heparan sulfate ; heparinase C ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 570
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Cytokines and Chemokines in SARS-CoV-2 Infections-Therapeutic Strategies Targeting Cytokine Storm.

    Pum, Alexandra / Ennemoser, Maria / Adage, Tiziana / Kungl, Andreas J

    Biomolecules

    2021  Volume 11, Issue 1

    Abstract: The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal ...

    Abstract The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal consequences. Although several factors of this infection and its consequences are not completely clear, the presence and involvement of specific chemokines is undoubtedly crucial for the development and progression of COVID-19. Cytokine storm and the often-resulting cytokine release syndrome (CRS) are pathophysiological hallmarks in COVID-19 infections related to its most severe and fatal cases. In this hyperinflammatory event, chemokines and other cytokines are highly upregulated and are therefore not fulfilling their beneficial function in the host response anymore but causing harmful effects. Here, we present the recent views on the involvement of chemokines and selected cytokines in COVID-19 and the therapeutics currently in clinical development targeting or interfering with them, discussing their potentials in the treatment of COVID-19 infections.
    MeSH term(s) COVID-19/immunology ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/immunology ; Cytokines/immunology ; Humans ; SARS-CoV-2 ; COVID-19 Drug Treatment
    Chemical Substances Cytokines
    Language English
    Publishing date 2021-01-12
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom11010091
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  6. Article ; Online: Synthesis and characterization of colloidal gold particles as labels for antibodies as used in lateral flow devices.

    Cvak, Barbara / Pum, Dietmar / Molinelli, Alexandra / Krska, Rudolf

    The Analyst

    2012  Volume 137, Issue 8, Page(s) 1882–1887

    Abstract: Based on well established citrate reduction protocols for the synthesis of colloidal gold particles, this work focuses on the characterization of these colloids for further use as color labels in lateral flow devices. A reproducible production method has ...

    Abstract Based on well established citrate reduction protocols for the synthesis of colloidal gold particles, this work focuses on the characterization of these colloids for further use as color labels in lateral flow devices. A reproducible production method has been developed for the synthesis of well characterized colloidal gold particles to be employed in Lateral Flow Devices (LFDs). It has been demonstrated that when undertaking chemical reduction of gold salts with sodium citrate, the amount of reducing agent employed could be used to directly control the size of the resultant particles. A protocol was thereby developed for the synthesis of colloidal gold particles of pre-defined diameters in the range of 15 to 60 nm and of consistent size distribution. The absorption maxima (λ(max)) of the reaction solutions were analyzed by UV/VIS measurements to determine approximate particle sizes, which were confirmed with transmission electron microscopy (TEM) measurements. Colloidal gold particles of about 40 nm in diameter were synthesized and used for labeling monoclonal anti-mycotoxin antibodies (e.g. zearalenone). To deduce the extent of antibody coupling to these particles, smaller colloids with 15 nm diameter were labeled with anti-species specific antibodies. Both solutions were mixed and then scanned by TEM to obtain information about the success of coupling.
    MeSH term(s) Antibodies/chemistry ; Colloids ; Gold/chemistry ; Microscopy, Electron, Transmission ; Spectrophotometry, Ultraviolet
    Chemical Substances Antibodies ; Colloids ; Gold (7440-57-5)
    Language English
    Publishing date 2012-04-21
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 210747-8
    ISSN 1364-5528 ; 0003-2654
    ISSN (online) 1364-5528
    ISSN 0003-2654
    DOI 10.1039/c2an16108g
    Database MEDical Literature Analysis and Retrieval System OnLINE

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