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Suicide behavior of target cells after binding with natural killer cells
G Arancia1, M C Sirianni, W Malorni
1Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
Abstract:
Human natural killer (NK) cell activity seems to be related to the integrity and function of the cytoskeletal apparatus. It has been hypothesized that microfilaments and microtubules play a pivotal role. In particular, the binding of the NK cell to the target cell requires microfilament integrity, and the lysis of bound targets seems to depend on microtubule assembly. We focused on the changes occurring in cytoskeletal elements and surface structures of NK cells and of target cells highly sensitive to NK activity (K562). Our observations, performed by fluorescence and scanning electron microscopy, besides confirming a rearrangement of the cytoskeletal apparatus in the effector cell, provide evidence that target cell cytoskeletal elements are involved in NK cell function. In K562 cells, after binding with NK cells, there is marginal rearrangement of actin and polarization of tubulin and vimentin in the contact regions, accompanied by modification of surface structures. These findings suggest that the target cell plays an active role in its own death by participating in the formation of an extended area of intimate contact with the killer cell. In addition, they lend credence to the surprising proposal that NK cells may induce a suicide mechanism in target cells.
Insights
Natural killer (NK) cells utilize cytoskeletal rearrangements for target cell binding and lysis. This study reveals target cells also actively participate in NK cell interactions, suggesting a role in their own demise.
Area of Science:
- Immunology
- Cell Biology
- Cytoskeletal Dynamics
Background:
- Natural killer (NK) cell activity is crucial for immune surveillance and relies on the effector cell's cytoskeletal integrity.
- Microfilaments and microtubules are hypothesized to play key roles in NK cell binding and target cell lysis.
Purpose of the Study:
- To investigate the dynamic changes in cytoskeletal elements and surface structures of NK cells and K562 target cells during immune interactions.
- To elucidate the specific roles of microfilaments and microtubules in NK cell-mediated cytotoxicity.
Main Methods:
- Utilized fluorescence microscopy to observe cytoskeletal rearrangements in NK and K562 cells.
- Employed scanning electron microscopy to analyze surface structure modifications during cell-cell contact.
- Focused on actin, tubulin, and vimentin dynamics in both effector and target cells.
Main Results:
- Confirmed cytoskeletal rearrangement in NK effector cells upon target cell engagement.
- Observed marginal actin rearrangement and polarization of tubulin and vimentin in K562 target cells at the contact site.
- Documented modifications in the surface structures of K562 cells following NK cell binding.
Conclusions:
- Target cells actively participate in NK cell-mediated killing by reorganizing their cytoskeleton and modifying surface structures.
- The formation of an extended contact area involves active contributions from the target cell.
- NK cells may induce apoptosis or a 'suicide mechanism' in target cells through these complex interactions.