Natural antibodies and tissue injury

May 15 2007

Lack of blood flow to the intestines during surgery, to the heart during a heart attack or to the brain during a stroke can cause damage to the organ involved.

However, more damage occurs when the blood returns to the organ.

Sherry Fleming, assistant professor of biology at Kansas State University, thinks she knows why and is working to find therapeutic ways to prevent this damage. Fleming has received various funding for her research, including, most recently, a five-year, $1.79 million grant from the National Institute of Allergy and Infectious Diseases for "Natural Antibodies and Tissue Injury."

Fleming said a type of white blood cell called a B cell makes antibodies; some of these antibodies are responsible for damage to organs after ischemia, or lack of blood flow. When an organ is deprived of blood and oxygen, white blood cells and antibodies cannot enter. These cells "clean up" when a part of the body is damaged and if they are not available at the time when the damage is occurring to constantly work on the problem, they tend to do more harm than good when they are finally let in, like after a heart attack.

The antibodies bind and identify the damaged tissue for removal by the white blood cells when they return to the organ. Fleming is working to isolate B cells that make the antibodies that bind and identify the damaged tissue. When too many antibodies are bound, proteins in the blood called complement bind the antibodies and kill more cells indiscriminately. This leads to more tissue damage.

However, the goal is not to stop all B cells from making antibodies since many of them are helpful to the immune system; only some are harmful.

"We have performed tests without antibodies and the damage doesn't occur," Fleming said. "We want to figure out which B cells are making the harmful antibodies and stop them." Stopping them includes delivering other therapeutic molecules that prevent complement proteins from damaging tissue.

Fleming's research will be beneficial to those experiencing intestinal ischemia, which she said can have a mortality rate of 70 percent to 100 percent. This research could also help heart attack and hemorrhage victims and those with lupus.

Hemorrhage is similar to ischemia in certain ways, Fleming said. When one part of the body is bleeding profusely, the body directs the blood from the non-vital organs, including the intestines, and sends more blood to the lungs, heart and brain. Because of this, some organs experience ischemia-like conditions when the body hemorrhages.

In addition, the same antibodies that harm tissue after blood flow is resumed are also found in great numbers in people with lupus, an autoimmune disease. Finding ways to curb damage due to the excess antibodies may be part of a cure for this affliction, Fleming said.

"We'd like to find out why someone with an autoimmune disease has these antibodies to begin with," she said.

Students who participate in research with Fleming include Susie Suozzo, senior in biology, Lansing; Lauren Phillips, junior in biology, Olathe; Diane Hylton, sophomore in nutritional sciences, Tecumseh; and Sara Brogan, graduate student in biology, Winfield. Lynn Tustin, research associate, biology, is also involved with the work. Tustin has a doctorate in physiology from K-State.

Fleming's work is also funded by the American Heart Association, Department of Defense, K-State Center for Epithelial Function in Health and Disease, Kansas IDeA Network of Biomedical Research Excellence, K-State's Terry C. Johnson Center for Basic Cancer Research and a National Science Foundation-Advance Grant. She has presented on the research at the annual meeting of the Society for Leukocyte Biology.