LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: COVID-19 generates hyaluronan fragments that directly induce endothelial barrier dysfunction

    Kimberly A. Queisser / Rebecca A. Mellema / Elizabeth A. Middleton / Irina Portier / Bhanu Kanth Manne / Frederik Denorme / Ellen J. Beswick / Matthew T. Rondina / Robert A. Campbell / Aaron C. Petrey

    JCI Insight, Vol 6, Iss

    2021  Volume 17

    Abstract: Vascular injury has emerged as a complication contributing to morbidity in coronavirus disease 2019 (COVID-19). The glycosaminoglycan hyaluronan (HA) is a major component of the glycocalyx, a protective layer of glycoconjugates that lines the vascular ... ...

    Abstract Vascular injury has emerged as a complication contributing to morbidity in coronavirus disease 2019 (COVID-19). The glycosaminoglycan hyaluronan (HA) is a major component of the glycocalyx, a protective layer of glycoconjugates that lines the vascular lumen and regulates key endothelial cell functions. During critical illness, as in the case of sepsis, enzymes degrade the glycocalyx, releasing fragments with pathologic activities into circulation and thereby exacerbating disease. Here, we analyzed levels of circulating glycosaminoglycans in 46 patients with COVID-19 ranging from moderate to severe clinical severity and measured activities of corresponding degradative enzymes. This report provides evidence that the glycocalyx becomes significantly damaged in patients with COVID-19 and corresponds with severity of disease. Circulating HA fragments and hyaluronidase, 2 signatures of glycocalyx injury, strongly associate with sequential organ failure assessment scores and with increased inflammatory cytokine levels in patients with COVID-19. Pulmonary microvascular endothelial cells exposed to COVID-19 milieu show dysregulated HA biosynthesis and degradation, leading to production of pathological HA fragments that are released into circulation. Finally, we show that HA fragments present at high levels in COVID-19 patient plasma can directly induce endothelial barrier dysfunction in a ROCK- and CD44-dependent manner, indicating a role for HA in the vascular pathology of COVID-19.
    Keywords COVID-19 ; Vascular biology ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: IFITM3 regulates fibrinogen endocytosis and platelet reactivity in nonviral sepsis

    Robert A. Campbell / Bhanu Kanth Manne / Meenakshi Banerjee / Elizabeth A. Middleton / Abigail Ajanel / Hansjorg Schwertz / Frederik Denorme / Chris Stubben / Emilie Montenont / Samantha Saperstein / Lauren Page / Neal D. Tolley / Diana L. Lim / Samuel M. Brown / Colin K. Grissom / Douglas W. Sborov / Anandi Krishnan / Matthew T. Rondina

    The Journal of Clinical Investigation, Vol 132, Iss

    2022  Volume 23

    Abstract: Platelets and megakaryocytes are critical players in immune responses. Recent reports suggest infection and inflammation alter the megakaryocyte and platelet transcriptome to induce altered platelet reactivity. We determined whether nonviral sepsis ... ...

    Abstract Platelets and megakaryocytes are critical players in immune responses. Recent reports suggest infection and inflammation alter the megakaryocyte and platelet transcriptome to induce altered platelet reactivity. We determined whether nonviral sepsis induces differential platelet gene expression and reactivity. Nonviral sepsis upregulated IFN-induced transmembrane protein 3 (IFITM3), an IFN-responsive gene that restricts viral replication. As IFITM3 has been linked to clathrin-mediated endocytosis, we determined whether IFITM3 promoted endocytosis of α-granule proteins. IFN stimulation enhanced fibrinogen endocytosis in megakaryocytes and platelets from Ifitm+/+ mice, but not Ifitm–/– mice. IFITM3 overexpression or deletion in megakaryocytes demonstrated IFITM3 was necessary and sufficient to regulate fibrinogen endocytosis. Mechanistically, IFITM3 interacted with clathrin and αIIb and altered their plasma membrane localization into lipid rafts. In vivo IFN administration increased fibrinogen endocytosis, platelet reactivity, and thrombosis in an IFITM-dependent manner. In contrast, Ifitm–/– mice were completely rescued from IFN-induced platelet hyperreactivity and thrombosis. During murine sepsis, platelets from Ifitm+/+ mice demonstrated increased fibrinogen content and platelet reactivity, which was dependent on IFN-α and IFITMs. Platelets from patients with nonviral sepsis had increases in platelet IFITM3 expression, fibrinogen content, and hyperreactivity. These data identify IFITM3 as a regulator of platelet endocytosis, hyperreactivity, and thrombosis during inflammatory stress.
    Keywords Hematology ; Inflammation ; Medicine ; R
    Subject code 570 ; 630
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Homogeneous surrogate virus neutralization assay to rapidly assess neutralization activity of anti-SARS-CoV-2 antibodies

    Sun Jin Kim / Zhong Yao / Morgan C. Marsh / Debra M. Eckert / Michael S. Kay / Anna Lyakisheva / Maria Pasic / Aiyush Bansal / Chaim Birnboim / Prabhat Jha / Yannick Galipeau / Marc-André Langlois / Julio C. Delgado / Marc G. Elgort / Robert A. Campbell / Elizabeth A. Middleton / Igor Stagljar / Shawn C. Owen

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 9

    Abstract: Neutralisation assays are key to understanding immune responses to SARS-CoV-2 infection or vaccination. Here, the authors report a surrogate virus neutralization assay called Neu-SATiN, which measures neutralization directly from sera, and allows easy ... ...

    Abstract Neutralisation assays are key to understanding immune responses to SARS-CoV-2 infection or vaccination. Here, the authors report a surrogate virus neutralization assay called Neu-SATiN, which measures neutralization directly from sera, and allows easy adaptation to variant-specific testing.
    Keywords Science ; Q
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis

    Shubhanshi Trivedi / Daniel Labuz / Cole P Anderson / Claudia V Araujo / Antoinette Blair / Elizabeth A Middleton / Owen Jensen / Alexander Tran / Matthew A Mulvey / Robert A Campbell / J Scott Hale / Matthew T Rondina / Daniel T Leung

    eLife, Vol

    2020  Volume 9

    Abstract: Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during ... ...

    Abstract Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-γ and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients at sepsis presentation were significantly reduced in frequency compared to healthy donors, and were more activated, with decreased IFN-γ production, compared to both healthy donors and paired 90-day samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis.
    Keywords sepsis ; MAIT cells ; innate-like T cell ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

    Trevor P. Fidler / Robert A. Campbell / Trevor Funari / Nicholas Dunne / Enrique Balderas Angeles / Elizabeth A. Middleton / Dipayan Chaudhuri / Andrew S. Weyrch / E. Dale Abel

    Cell Reports, Vol 20, Iss 4, Pp 881-

    2017  Volume 894

    Abstract: Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. ... ...

    Abstract Anucleate platelets circulate in the blood to facilitate thrombosis and diverse immune functions. Platelet activation leading to clot formation correlates with increased glycogenolysis, glucose uptake, glucose oxidation, and lactic acid production. Simultaneous deletion of glucose transporter (GLUT) 1 and GLUT3 (double knockout [DKO]) specifically in platelets completely abolished glucose uptake. In DKO platelets, mitochondrial oxidative metabolism of non-glycolytic substrates, such as glutamate, increased. Thrombosis and platelet activation were decreased through impairment at multiple activation nodes, including Ca2+ signaling, degranulation, and integrin activation. DKO mice developed thrombocytopenia, secondary to impaired pro-platelet formation from megakaryocytes, and increased platelet clearance resulting from cytosolic calcium overload and calpain activation. Systemic treatment with oligomycin, inhibiting mitochondrial metabolism, induced rapid clearance of platelets, with circulating counts dropping to zero in DKO mice, but not wild-type mice, demonstrating an essential role for energy metabolism in platelet viability. Thus, substrate metabolism is essential for platelet production, activation, and survival.
    Keywords glucose ; metabolism ; glucose transporters ; platelet ; megakaryocyte ; calpain ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2017-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

    Trevor P. Fidler / Robert A. Campbell / Trevor Funari / Nicholas Dunne / Enrique Balderas Angeles / Elizabeth A. Middleton / Dipayan Chaudhuri / Andrew S. Weyrich / E. Dale Abel

    Cell Reports, Vol 21, Iss 6, p

    2017  Volume 1705

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2017-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function

    Trevor P. Fidler / Robert A. Campbell / Trevor Funari / Nicholas Dunne / Enrique Balderas Angeles / Elizabeth A. Middleton / Dipayan Chaudhuri / Andrew S. Weyrch / E. Dale Abel

    Cell Reports, Vol 20, Iss 9, p

    2017  Volume 2277

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2017-08-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top