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'Natural killer' white blood cells: modus operandi

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A team of EU-funded scientists from the United Kingdom has revealed in a new study how white blood cells kill diseased tissue using deadly granules.

The team of researchers, from Imperial College London and the University of Oxford, set out in the journal PLoS Biology how they used 'optical' laser tweezers and a super-resolution microscope to view the inner workings of white blood cells at a resolution never before achieved by scientists.

The study, which was funded in part by a Marie Curie Intra-European Fellowship grant under the EU's Seventh Framework Programme (FP7), looked at a type of white blood cell called a natural killer (NK) cell that protects the body by identifying and killing diseased tissue. The team found that to create a hole through which it delivers deadly enzyme-filled granules to kill diseased tissue, the NK cell rearranges its 'scaffolding' of actin proteins on the inside of its membrane.

One of the study researchers, Dr Alice Brown from Imperial College London, says: 'These previously undetectable events inside cells have never been seen in such high resolution. It is truly exciting to observe what happens when an NK cell springs into action.'

Gaining a deeper understanding of how NK cells identify which tissues to kill and initiate the killing process could lead to better health care and the development of new medical treatments, scientists hope. NK cells are important in our immune response to viruses and rogue tissues like tumours. They may also play a role in the outcome of bone marrow transplants by determining whether a recipient's body rejects or accepts the donated tissue.

Another study author from Imperial College London, Professor Daniel Davis comments: 'In the future, drugs that influence where and when NK cells kill could be included in medical treatments, such as the targeted killing of tumours. They may also prove useful in preventing the unwanted destruction by NK cells that may occur in transplant rejection or some auto-immune diseases.'

The researchers immobilised an NK cell and its target using a pair of 'optical' laser tweezers so that the microscope could capture all the action at the interface between the cells. Next they observed the inside of the NK cell as the actin filaments parted to create a tiny portal and the enzyme-filled granules moved to the portal, ready to pass out of the NK cell and onto the target ready to kill it.

This contact takes place in a space that is only a hundredth of a millimetre across; in addition, the miniscule actin proteins and granules change position continuously over the few minutes from initial contact until the target is killed. In such rapidly changing conditions, the microscope needs to be able to capture images quickly enough and in high enough visual detail in order to reveal their activity.

It was for this reason that the team used the specially developed laser tweezers to get the best view of the action. It gave them never before seen views inside living NK cells capturing a super-resolution 3D image of cell structures at twice the normal resolution of a conventional light microscope. This method maximises the amount of light captured from the specimen while at the same time minimises the amount of stray light inside the apparatus.

Professor Paul French from Imperial College London was one of the researchers who worked on the development of the special microscopic equipment.
'Using laser tweezers to manipulate the interface between live cells into a horizontal orientation means our microscope can take many images of the cell contact interface in rapid succession. This has provided an unprecedented means to directly see dynamic molecular processes that go on between live cells,' he explains.

Marie Curie Intra-European Fellowships are individual fellowships that provide advanced training tailored to researchers' individual needs with the aim of adding different scientific competencies to their research armoury. This focus on development and progression allows Marie Cure grant recipients to further their career and advance in their field