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Updated: Dec 9, 2025
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Teasing Out the Interplay Between Natural Killer Cells and Nociceptor Neurons
Published on: June 30, 2022
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Synaptic secretion from human natural killer cells is diverse and includes supramolecular attack particles
Ashley R Ambrose1, Khodor S Hazime1, Jonathan D Worboys1
1The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, M13 9NT Manchester, United Kingdom.
Summary
Natural killer (NK) cells release various molecules, including perforin and granzyme B, through immune synapses. This study reveals NK cells secrete diverse structures, such as supramolecular attack particles (SMAPs), unexpectedly differing from cytotoxic T lymphocytes (CTLs).
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Natural killer (NK) cells are crucial for innate immunity, identifying and eliminating unhealthy cells via immune synapses.
- Upon activation, NK cells and cytotoxic T lymphocytes (CTLs) release cytotoxic proteins like perforin and granzyme B.
- These proteins can be packaged in specialized secretory structures, including supramolecular attack particles (SMAPs), which have been observed in CTLs complexed with thrombospondin-1 (TSP-1).
Purpose of the Study:
- To investigate the nature and diversity of synaptic secretions from individual NK cells.
- To compare NK cell secretory products, specifically SMAPs, with those of CTLs.
Main Methods:
- Utilized an advanced imaging technique to precisely locate and analyze secretions from individual NK cells after their removal.
- Assessed the composition of NK cell synaptic secretions, including vesicles and SMAPs, for the presence of TSP-1, perforin, and granzyme B.
- Quantified and characterized SMAPs secreted by NK cells and compared them to those from CTLs.
Main Results:
- NK cell synaptic secretion, triggered by NKp30 or NKG2D receptor ligation, comprises both vesicles and SMAPs.
- These NK cell SMAPs and vesicles contain TSP-1, perforin, and granzyme B.
- Individual NK cells exhibited varied secretion patterns, releasing SMAPs, CD63+ vesicles, or a combination of both.
- While NK cells and CTLs secreted a comparable number of SMAPs, NK cell-derived SMAPs were significantly larger.
Conclusions:
- NK cell immune synapse secretion is more diverse than previously understood, involving distinct populations of vesicles and SMAPs.
- The presence of TSP-1 in NK cell SMAPs and the observed differences in SMAP size compared to CTLs highlight unique aspects of NK cell cytotoxic mechanisms.
- These findings expand our understanding of NK cell effector functions and intercellular communication during immune responses.
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