Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The Janus-like role of neuraminidase isoenzymes in inflammation

View ORCID ProfileMd. Amran Howlader, View ORCID ProfileEkaterina P. Demina, Suzanne Samarani, View ORCID ProfileTianlin Guo, View ORCID ProfileAli Ahmad, View ORCID ProfileAlexey V. Pshezhetsky, View ORCID ProfileChristopher W. Cairo
doi: https://doi.org/10.1101/2021.07.14.452400
Md. Amran Howlader
1Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Md. Amran Howlader
Ekaterina P. Demina
2Sainte-Justine Hospital Research Center, Division of Medical Genetics, University of Montreal, Montreal, Quebec, H3T 1C5, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ekaterina P. Demina
Suzanne Samarani
2Sainte-Justine Hospital Research Center, Division of Medical Genetics, University of Montreal, Montreal, Quebec, H3T 1C5, Canada
4Department of Microbiology, Infectious Diseases & Immunology, Sainte-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, H3T 1C5, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tianlin Guo
1Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tianlin Guo
Ali Ahmad
2Sainte-Justine Hospital Research Center, Division of Medical Genetics, University of Montreal, Montreal, Quebec, H3T 1C5, Canada
4Department of Microbiology, Infectious Diseases & Immunology, Sainte-Justine Hospital Research Center, University of Montreal, Montreal, Quebec, H3T 1C5, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ali Ahmad
Alexey V. Pshezhetsky
2Sainte-Justine Hospital Research Center, Division of Medical Genetics, University of Montreal, Montreal, Quebec, H3T 1C5, Canada
3Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, H3A0C7, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alexey V. Pshezhetsky
  • For correspondence: alexei.pchejetski@umontreal.ca ccairo@ualberta.ca
Christopher W. Cairo
1Department of Chemistry, University of Alberta, Edmonton, Alberta, T6G 2G2, Canada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Christopher W. Cairo
  • For correspondence: alexei.pchejetski@umontreal.ca ccairo@ualberta.ca
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The processes of activation, extravasation, and migration of immune cells to a site are early and essential steps in the induction of an acute inflammatory response. These events are part of the inflammatory cascade which involves multiple regulatory steps. Using a murine air-pouch model of inflammation with LPS as an inflammation inducer we demonstrate that isoenzymes of the neuraminidase family (NEU1, 3, and 4) play essential roles in this process acting as positive or negative regulators of leukocyte infiltration. Genetically knocked-out (KO) mice for different NEU genes (Neu1 KO, Neu3 KO, Neu4 KO, and Neu3/4 double KO mice) were induced with LPS, leukocytes at the site of inflammation were counted, and the inflamed tissue was analyzed using immunohistochemistry. Our data show that leukocyte recruitment was decreased in NEU1 and NEU3-deficient mice, while it was increased in NEU4-deficient animals. Consistent with these results, systemic levels of pro-inflammatory cytokines and those in pouch exudate were reduced in Neu1 and increased in Neu4 KO mice. We found that pharmacological inhibitors specific for NEU1, NEU3, and NEU4 isoforms also affected leukocyte recruitment. We conclude that NEU isoenzymes have distinct – and even opposing – effects on leukocyte recruitment, and therefore warrant further investigation to determine their mechanisms and importance as regulators of the inflammatory cascade.

Competing Interest Statement

MAH, CWC, TG, AVP are inventors on patent applications related to this work.

  • Abbreviations

    BW
    body weight
    BMDM
    bone marrow-derived macrophage
    DKO
    double knock out
    IN1
    inhibitor of NEU1 (CG14600)
    IN3
    inhibitor of NEU3 (CG22600)
    IN4
    inhibitor of NEU4 (CY16600)
    KO
    knock out
    LPS
    lipopolysaccharide
    MO
    monocytes
    MΦ
    macrophages
    NE
    neutrophil
    NEU1
    neuraminidase 1
    NEU3
    neuraminidase 3
    NEU4
    neuraminidase 4
    NK
    natural killer cells
    WT
    wild type
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
    Back to top
    PreviousNext
    Posted July 14, 2021.
    Download PDF

    Supplementary Material

    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    The Janus-like role of neuraminidase isoenzymes in inflammation
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    The Janus-like role of neuraminidase isoenzymes in inflammation
    Md. Amran Howlader, Ekaterina P. Demina, Suzanne Samarani, Tianlin Guo, Ali Ahmad, Alexey V. Pshezhetsky, Christopher W. Cairo
    bioRxiv 2021.07.14.452400; doi: https://doi.org/10.1101/2021.07.14.452400
    Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
    Citation Tools
    The Janus-like role of neuraminidase isoenzymes in inflammation
    Md. Amran Howlader, Ekaterina P. Demina, Suzanne Samarani, Tianlin Guo, Ali Ahmad, Alexey V. Pshezhetsky, Christopher W. Cairo
    bioRxiv 2021.07.14.452400; doi: https://doi.org/10.1101/2021.07.14.452400

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Immunology
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (4680)
    • Biochemistry (10352)
    • Bioengineering (7670)
    • Bioinformatics (26325)
    • Biophysics (13521)
    • Cancer Biology (10682)
    • Cell Biology (15429)
    • Clinical Trials (138)
    • Developmental Biology (8496)
    • Ecology (12818)
    • Epidemiology (2067)
    • Evolutionary Biology (16848)
    • Genetics (11391)
    • Genomics (15474)
    • Immunology (10609)
    • Microbiology (25196)
    • Molecular Biology (10215)
    • Neuroscience (54447)
    • Paleontology (401)
    • Pathology (1668)
    • Pharmacology and Toxicology (2897)
    • Physiology (4341)
    • Plant Biology (9242)
    • Scientific Communication and Education (1586)
    • Synthetic Biology (2557)
    • Systems Biology (6777)
    • Zoology (1463)