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NEUTROPHIL SECRETION OF THE PROINFLAMMATORY CYTOKINE TNF VIA RECYCLING ENDOSOMES

  • Author / Creator
    Srivastava, Nutan
  • Neutrophils are highly abundant innate immune cells that are important in immediate responses to injury and infection, and secrete the proinflammatory cytokine tumor necrosis factor (TNF). Inflammatory cytokines have many potent effects and their excess or deficiency may have many clinical consequences. However, cytokine trafficking and secretion in neutrophils has not been well characterized. Recycling endosomes (REs) are specialized secretory compartments that perform multiple functions including trafficking of cytokines to cell surfaces, although these are not characterized in neutrophils. Our objective is to identify trafficking components in neutrophils that may contribute to cytokine secretion. This study presents data that shows that LPS induced 30-40% TNF secretion from stored sources, with the remainder newly synthesized. We also found that neutrophils possess REs as determined by transferrin uptake and VAMP-3 labeling. TNF also colocalized with REs, primary and secondary granules as well as early and late endosomes, suggesting multiple sites of TNF storage and trafficking in neutrophils. TNF colocalized with VAMP-3 around periphery of cells after 1 h stimulation with LPS, suggesting TLR4-induced TNF trafficking via REs. The present study provides evidence that movement of TNF+VAMP-3+ vesicles towards the cell periphery in response to LPS. This suggests that neutrophils utilize REs for trafficking of TNF to the cell surface in response to TLR4 signaling. These findings contribute to our understanding of how neutrophils package, transport, and release cytokines.

  • Subjects / Keywords
  • Graduation date
    2015-06
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3P69J
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Medicine
  • Supervisor / co-supervisor and their department(s)
    • Dr. Paige lacy
  • Examining committee members and their departments
    • Dr. Joel Dacks (Department of Cell Biology)
    • Dr. Paige Lacy (Department of Medicine)
    • Dr. Michael Sean McMurtry (Department of Medicine)
    • Dr. Gary Eitzen (Department of Cell Biology)
    • Dr. Allan Murray (Department of Medicine)