Nagarkattis discover "killer" immune cells

The treatment for cancer can often be as life threatening as the disease itself.

Mitzi Nagarkatti, a professor in the Virginia-Maryland Regional College of Veterinary Medicine, and biology professor Prakash Nagarkatti have broken ground in this area by discovering "killer" immune cells generated by cancer treatment.

In a healthy person, the immune system works in tandem with the body's defenses fighting infection and disease. The cancer fighting drug Interleukin-2 contains a large dose of the same immune molecule. The problem occurs when the immune cells--lymphocytes--also attack the endothelial cells that line and protect blood vessels. Once those cells are killed, blood vessels develop leaks that can lead to edema, shock, and even death. Up to now, the only option has been to monitor signs of edema and stop chemotherapy when blood vessel leaks were detected.

Prior to the Nagarkatti research, scientists thought that the blood vessel damage was being done by the cancer, Mitzi Nagarkatti says. The Nagarkattis have no doubt that it is these killer immune cells that are responsible for the vascular leaking after viewing the occurring cell damage with electron microscopes and a flow cytometer.

To prevent the cell death, the husband-wife team sought to find and disable the specific molecules that must be present for the interaction between the lymphocytes and endothelial cells to take place. They discovered that mice genetically engineered to lack the CD 44 molecule didn't experience the vascular leakage caused by injections of Interleukin-2. Now the Ngarkattis are attempting to block CD 44 from being used in the cell-destruction process.

The Nagarkattis' research will have an impact on other situations in which immune cells attack blood vessels, such as after organ transplants and in auto-immune diseases like lupus. The Nagarkattis were recently awarded a $500,000 grant from the National Institutes of Health for the project.

Tobacco to the rescue?

Can tobacco provide the cure for disease? Strange as it may seem, research that could lead to a tobacco-based industry growing human pharmaceuticals has already begun in fields across Virginia.

Virginia Tech scientists, along with a Blacksburg biotechnology company, are developing special methods required to grow the transgenic tobacco that could bring new, high-value use to hundreds of acres of tobacco, under an $8.8 million grant from the U.S. Department of Commerce.

The plant's large number of leaves and high seed production make it ideal for use in producing pharmaceuticals. It is also one of the easiest plants to modify genetically, in this case modified to carry a piece of DNA with the information encoded on how to build a human protein.

Already scientists here have used the transgenic tobacco to produce human protein C, which can be refined for use in blood clotting applications. Another human enzyme genetically engineered into the tobacco can be used to treat a life-threatening disease that affects the body's ability to break down fats.

Researchers will eventally plant tens of thousands of transgenic tobacco seedlings at the university's research stations at Blackstone and Glade Springs. Greenhouse experiments and laboratory analyses will take place at Virginia Tech. The first crop is being developed with a "reporter gene" that will enable scientists to rapidly assess the performance of the plant under a variety of growing conditions.

In addition to the federal grant, the project has received a $554,000 commitment from the Virginia General Assembly for the first phase of the project. An additional $200,000 is pledged for future research.
Virginia Tech Magazine

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