"The activities of neutrophils are very important for our survival, so they are the subject of significant scientific study," said Dr. Ley. While some scientists study their migration out of the blood vessel, Dr. Ley's lab has focused on how neutrophils adhere to the blood vessel wall. "This is important because it provides an opportunity to develop new treatments based on modulating or blocking one of the steps in the adhesion cascade," said Dr. Ley, noting that earlier studies have shown that blocking even one of the steps can severely reduce neutrophil recruitment.
While Dr. Ley has previously shown how neutrophils adhere when blood flow is slow, his latest study reveals that neutrophils use long membrane tethers at the front of the cell, termed "slings," to slow down during high blood flow. The cells do this by separating their cytoskeleton from the cellular membrane, wrapping the sling around themselves like a lasso and then digging their hooks into the blood vessel wall, said Dr. Ley. High blood flow occurs during inflammation, when the body rushes immune cells to a site to promote healing. Inflammation is a normal part of the healing process, but is unwanted in certain diseases.
"For these cells, adhering under high shear is like being in a huge wind storm," said Dr. Ley. "The challenge in this storm is not to get blown away."
Dr. Ley's studies could prove valuable in helping scientists understand how to reduce adhesion, where inflammation is unwanted, such as in heart or autoimmune disease, or to enhance the process, where more neutrophils are desired, such as in bacterial infections like MRSA. "The body needs to have enough neutrophils to fight off bacteria faster than they can grow," he said. "Better understanding of neutro
|Contact: Bonnie Ward|
La Jolla Institute for Allergy and Immunology