Join us on Essential Immunity Player Might Be Target for New Transplantation Rejection Therapies
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another culprit to the body's efforts to reject transplanted tissues and organs.
A new perspective on how the body reacts to transplanted tissues and organs is coming into focus, and William M. Baldwin, III , MD , PhD, Immunology, says it implicates platelets as a major factor in rejection.
There are two sources for transplanted tissues: human-to-human allografts (e.g., donated kidneys) and animal-to-human xenografts (e.g., heart valves from pigs). The recipient's body generally responds to transplantation in two ways. First, the body reacts to the actual surgery as it would to any injury, by enlisting platelets to stop the bleeding and white blood cells to fight potential infection. These platelets come from both the recipient (often a reaction to the disease that caused the need for a transplant in the first place or in response to the mechanical devices that are used to keep the patient alive until transplantation) and from the organ donor (“imported” with the tissue or organ). After adhering to blood vessels to prevent bleeding, platelets release molecules that signal the immune system's white blood cells to help protect against infections.
Second, because the new organ is foreign tissue, considered by the patient's body to be “non-self,” the recipient mounts an immunological response not unlike the kind used for attacking viruses or bacteria. This immunological response injures the blood vessels of the transplant, which leads to platelets adhering to the vessels and signaling even more white cells.
While these reactions ordinarily involve what you want platelets to do, when it comes to organ transplants, this pro-inflammatory function exceeds the initial wound-healing requirement, and platelets begin doing more harm than good.
“Our review of the literature, including our own studies, makes a case for the platelet being an integral component of graft rejection. There has been some appreciation of platelets being relevant to xenografts, but this isn't the conventional view, particularly in allografts,” Dr. Baldwin said. “So this new view of the current knowledge represents a new paradigm.
“There's the potential for new therapies that target platelets to keep them from contributing to the pro-inflammatory response that result in organ and tissue rejection,” he said. “But we'll need to balance the benefits of that type of therapy with the need to maintain the patient's ability to clot blood.”
Dr. Baldwin's research team includes Allan D. Kirk, MD, of Emory University, and Craig N. Morrell, DVM, PhD, of Johns Hopkins University School of Medicine. The findings appeared in the American Journal of Transplantation (www.amjtransplant.com/ 2009 Jan;9:14-22.). The researchers were supported by grants from the National Institutes of Health, the Georgia Research Alliance, and the McKelvey Foundation.