Packed Red Blood Cell-Associated Arginine Depletion is Mediated by Arginase

• DOI: 10.1097/ta.0b013e31814b2b17
• Publication Date: 2009-03-05T00:35:27Z
• Authors: Andrew Bernard; Cynthia Meier; Nicholas Lopez; John May; Phillip Chang; Bernard Boulanger; Paul Kearney
• Keywords: 0301 basic medicine; Plasma; 03 medical and health sciences; Erythrocytes; Arginase; Cell Culture Techniques; Immune Tolerance; Humans; Amino Acids; Arginine; Erythrocyte Transfusion; 3. Good health

Background: Packed red blood cells (PRBCs) transfusion is associated with immune suppression, but these mechanisms are incompletely understood. PRBCs contain arginase, an enzyme that converts arginine to ornithine, and known limit availability suppress cellular immunity. We sought determine whether PRBC arginase causes depletion, potentially contributing immunosuppression. Methods: A model of was designed by adding either centrifuged acellular supernatant from the unit (plasma) or total fluid (plasma+RBC [red cells]) cell culture media. Through institutional review board-approved protocol, units were isolated processed accredited bank stored at 4°C. Leukoreduced aliquots withdrawn every 5 days 7 for 42 days. Cell cultures created standard Roswell Park Memorial Institute media, controlling level 80 μmol/L (approximating human serum), 20% plasma plasma+RBC. An irreversible blocker (nor-N-ω-OH-l-arginine) added selected cultures. After 24 hours, activity measured ornithine synthesis, amino acid levels using mass spectroscopy. Results: Culture increased both plasma+RBC, plasma+RBC this did not reach statistical significance. Arginine decreased in containing PRBC, as compared control Addition nor-N-ω-OH-l-arginine significantly activity, restored levels, diminished synthesis. Conclusions: Arginase present depletion. Depletion a potential novel mechanism