Plasma from aged stored red blood cells delays neutrophil apoptosis and primes for cytotoxicity: Abrogation by poststorage washing but not prestorageleukoreduction

Background: Blood transfusion-particularly that of older stored red blood c ells (RBCs)-is an independent risk factor for postinjury multiple organ fai lure. Immunomodulatory effects of RBC transfusion include neutrophil (PMN) priming for cytotoxicity, an effect exacerbated by longer RBC storage times . We have found that delayed PMN apoptosis in trauma patients is provoked b y transfusion, independent of injury severity. We hypothesized that aged st ored RBCs delay PMN apoptosis, but that prestorage leukodepletion or postst orage washing could abrogate the effect. Methods: Healthy volunteers each donated 1 unit of blood, One half was leuk odepleted, and RBC units were processed in the usual fashion and stored at 4 degreesC, Aliquots were removed on days 1, 14, 21, and 42 and the plasma fraction isolated, Selected aliquots were washed with normal saline before plasma isolation. PMNs harvested from healthy controls were incubated (5% C O2, 37 degreesC) with unmodified, leukoreduced, or washed RBC plasma (20% p lasma/80% RPMI 1640), and apoptosis assessed by morphology after 24 hours. Apoptotic index (apoptotic PMNs/total PMNs) was compared. PMN priming for s uperoxide release was also assessed after plasma exposure. Results: PMN apoptosis was delayed by RBCs stored for 21 or 42 days. Presto rage leukodepletion did not alter the effect. However, washing 42-day-old R BCs abrogated the effect. PMN priming for superoxide was provoked by stored packed RBCs in an identical pattern to delayed apoptosis, Conclusion: Plasma from stored RBCs-even if leukoreduced-delays apoptosis a nd primes PMNs, The effect becomes evident at 21 days and worsens through p roduct outdate (42 days), but may be prevented by poststorage washing Infla mmatory agents contaminating stored blood likely mediate the effect Modific ation of transfusion practices (e.g., giving fresher or washed RBCs or bloo d substitutes) may attenuate adverse immunomodulatory effects of transfusio n in trauma patients.