Red Blood Cells Arginase and Immunosuppression

Arginase, a urea cycle enzyme that metabolizes arginine to ornithine, is an enzyme expressed in cells and tissues throughout the body. However, the urea cycle is incomplete in non-hepatic cells. Evidence produced by our group at University of Kentucky and others indicates that arginase in non-hepatic cells depletes arginine from tissue culture. Arginine is essential for normal cellular immunity as measured by Tlymphocyte proliferation and surface receptor expression. Therefore, non-hepatic arginase may contribute to immune dysfunction by depleting arginine. Trauma patients and surgical patients who receive blood transfusions lose normal cellular immunity. Arginine enhanced diets in the trauma and elective surgery patient has been shown to improve outcomes. The mechanisms for this are not well elucidated. Red blood cells contain a large amount of arginase that may become soluble in solution when packed red blood cells (PRBC) are stored, similar to the manner in which potassium levels increase. This, combined with the preliminary work above, supports the hypothesis that PRBC-induced immune dysfunction may occur through arginine depletion by soluble arginase in the donor unit. To begin testing this hypothesis, we have obtained samples of donor PRBC units (PRBCu). Plasma was separated by centrifugation and plasma arginase was measured as ornithine production. Healthy donor plasma was used as a comparison (Figure). PRBC plasma arginase activity was significantly greater (I8-fold) than control plasma.