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Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells

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Bryceson, Yenan T., March, Michael E., Barber, Domingo F., Ljunggren, Hans-Gustaf, Long, Eric O.·2005·The Journal of Experimental Medicine
DOI 10.1084/jem.20051143PMC PMC2213171
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Abstract

The relative contribution to cytotoxicity of each of the multiple NK cell activation receptors has been difficult to assess. Using Drosophila insect cells, which express ligands of human NK cell receptors, we show that target cell lysis by resting NK cells is controlled by different receptor signals for cytolytic granule polarization and degranulation. Intercellular adhesion molecule (ICAM)-1 on insect cells was sufficient to induce polarization of granules, but not degranulation, in resting NK cells. Conversely, engagement of the Fc receptor CD16 by rabbit IgG on insect cells induced degranulation without specific polarization. Lysis by resting NK cells occurred when polarization and degranulation were induced by the combined presence of ICAM-1 and IgG on insect cells. Engagement of receptor 2B4 by CD48 on insect cells induced weak polarization and no degranulation. However, coengagement of 2B4 and CD16 by their respective ligands resulted in granule polarization and cytotoxicity in the absence of leukocyte functional antigen-1–mediated adhesion to target cells. These data show that cytotoxicity by resting NK cells is controlled tightly by separate or cooperative signals from different receptors for granule polarization and degranulation.

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  • Cytolytic granule polarization and degranulation are two steps in lymphocyte-mediated cytotoxicity.

    “Cytolytic granule polarization and degranulation are two steps in lymphocyte-mediated cytotoxicity(Bryceson, March, Barber, Ljunggren, & Long, 2005;Mouchacca, Schmitt-Verhulst, & Boyer, 2013).”

    From Cuprizone‐induced demyelination triggers a CD8‐pronounced T cell recruitment (2021) · cites this paper as Bryceson, March, Barber, Ljunggren, & Long, 2005

    The Discussion states that granule polarization and degranulation are two steps in NK cell–mediated cytotoxicity. The citing sentence broadens this to lymphocyte-mediated cytotoxicity generally; although the paper notes that other cytotoxic lymphocytes also release cytolytic granules, it does not establish both steps for them. (LLM, conf=0.84)

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Metadata

Authors
Bryceson, Y. T., March, M. E., Barber, D. F., Ljunggren, H.-G., & Long, E. O.
Affiliations
  • National Institutes of Health (US)
  • Karolinska University Hospital (SE)
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2005-10-03
Volume
202
Issue
7
Pages
1001-1012
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20051143
PMC
PMC2213171
OpenAlex
W2084896925
Cited by
515
References
0
Citations by year
2026: 14 · 2025: 21 · 2024: 27 · 2023: 16 · 2022: 18 · 2021: 26 · 2020: 27 · 2019: 22 · 2018: 28 · 2017: 21 · 2016: 23 · 2015: 26 · 2014: 28 · 2013: 26 · 2012: 25
FWCI
7.28
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords
natural killer cells, degranulation, NK cell activation receptors, ICAM-1, CD16, CD48, LFA-1, cytotoxicity
MeSH terms
Signaling Lymphocytic Activation Molecule Family, Animals, Cell Adhesion, Cells, Cultured, Cloning, Molecular, Cytoplasmic Granules, Cytotoxicity Tests, Immunologic, Cytotoxicity, Immunologic, Drosophila, Enzyme-Linked Immunosorbent Assay, Humans, Killer Cells, Natural, Membrane Glycoproteins, Receptors, Immunologic, Signal Transduction, Antigens, CD, Receptors, IgG, DNA Primers, Intercellular Adhesion Molecule-1

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