Seek & Destroy:
Study of cell communication key to understanding the immune response.
Seek and destroy. That’s the job of the macrophage.
These large white blood cells exist in our bodies to engulf or digest foreign objects, typically a virus or bacteria. But when macrophages discover that they cannot eliminate a large object, such as an implanted glucose sensor, they call for help.
The macrophages communicate to other cells using proteins known as cytokines to signal for fibroblast cells to lay down collagen, a glue-like protein that can encase an object like a cocoon.
That immune response is beneficial, unless the foreign object being attacked is an implanted glucose monitor implanted in a diabetic person. The collagen build-up limits the life of the device and can put the diabetic patient at risk.
Julie Stenken, a bioanalytical chemist at the University of Arkansas, is working to change that.
As one of the world’s leading experts in the area of in vivo collection of the proteins known as cytokines, Stenken has spent more than a decade researching this cell-to-cell communication.
“When I started with the biomaterials and wound-healing work 12 years ago, I started reading more about cytokines,” Stenken said. “I soon realized I had landed in a diamond mine, research-wise. These signaling proteins are everywhere in the body and they are poorly understood and hard to measure directly from a living being. Our group is one of the few that measures cytokines on a daily basis.”
Her research, funded by the National Institutes of Health and others, has focused on cell response to implants such as glucose monitors and biomaterials. Her work has also moved toward disease response, looking at the role cytokines and cell communication play in diseases such as Alzheimer’s and Parkinson’s.
“Many of the problems that scientists have encountered in the development of long-term implanted sensors have been due to the lack of understanding of the host response to implanted materials,” Stenken said.
The number of diabetics in the United States is growing by an estimated 2 million a year. Extending the implanted glucose sensor’s lifetime is crucial to the future well-being of both juvenile and adult-onset diabetics.
“If you had a glucose sensor that was better integrated into the body, where you could reduce the number of finger-stick calibrations, people would be more compliant with their insulin doses,” she said. “It would be very helpful in managing their disease.”
Stenken’s research group uses a microdialysis probe that is placed under the skin of rats to mimic an implanted glucose sensor. The researchers use a unique process to infuse different agents through the probe to test ways to direct the macrophage response away from encapsulating an object to a slower, more gentle response associated with wound-healing.
Stenken also is using the microdialysis probe to study cytokines in the living brain. Cytokines are known to affect different human diseases, such as Alzheimer’s, Parkinson’s, alcoholism, epilepsy, multiple sclerosis and various psychiatric disorders.
“Cytokines are now considered the third-generation chemical communication system in the brain behind neurotransmitters and neuropeptides,” Stenken said. “People have been very interested in cytokines in the brain because they’re are known receptors and they show up in many neurodegenerative diseases, including Alzheimer’s and Parkinson’s.”
Stenken, the Twenty-First Century Chair in Proteomics in the J. William Fulbright College of Arts and Sciences, and her research group has received $3.4 million in grant funding for its work related to cytokine measurements and modulation.
“The chemistry that happens in living human beings is so complex and so intertwined,” she said. “I’m fascinated by the complexity of in vivo chemistry, and it’s that incredible complexity, difficulty, and significance of these types of projects that drives our research questions.”