Changes in band 3 structure as determinants of erythrocyte integrity during storage and survival after transfusion.

Abstract

Storage of erythrocytes for transfusion purposes is accompanied by a number of morphological and biochemical changes, the storage lesions. Some of these lesions, such as the almost complete, fast disappearance of 2,3-diphoshosphoglycerate and the relatively small, slow decrease in intracellular ATP, may be reversible. Other changes, such as the loss of haemoglobin, and of phospholipid and protein by vesiculation, are not1. Especially the irreversible lesions are likely to affect erythrocyte survival and function after transfusion. Elucidation of the underlying mechanisms may not only result in prolonged storage times, but also - and probably more importantly - in a higher quality of the erythrocyte transfusion product. One of the first requirements for a higher quality is prolonged survival time in vivo or, more specifically, a higher fraction of erythrocytes that survive the first 24 hours after transfusion. The data of recent studies, that used minor blood group antigens and compared the survival characteristics of various products in one and the same recipient, indicate that the percentage erythrocytes that is removed within a few hours after transfusion may be as high as 30%2. This fraction does not only represent nonfunctional erythrocytes, but also may be a major factor in the interaction between the transfused erythrocyte and the patient's immune system. The resulting pathological reactions may cause long-term transfusion side effects such as the development of anti-erythrocyte antibodies, especially in transfusion-dependent patients, and in patients with a chronic inflammation3–6. Since the pivotal studies showing that physiological removal of old erythrocytes is initiated by their specific recognition by the immune system7, it has become obvious to apply the knowledge of causes and effects of the aging process in vivo to the study of the changes that erythrocytes undergo during storage, an aging process in vitro. In fact, in one of the first attempts to mimick the physiological aging process, storage in blood bank-like conditions was the treatment that yielded the most complete set of biologically relevant aging parameters then available8. These parameters were concentrated on structural and functional changes in band 3, the anion exchanger and major protein of the erythrocyte membrane: increased breakdown as deduced from immunoblot patterns and decreased anion transport capacity as deduced from sulfate exchange characteristics8. Since then, our knowledge on composition and insight in the organisation of the erythrocyte membrane and the role of band 3 therein has vastly expanded. However, our knowledge on the molecular changes that band 3 undergoes during aging in vivo, the effects of these changes on binding of physiological, naturally occurring autoantibodies, and on the induction of pathological autoantibodies, has lagged behind. This hampers a critical evaluation of claims on the occurrence of erythrocyte aging during storage8–10. Here we will review the data that are presently available on changes in band 3 structure and function during storage in blood bank conditions, focusing on their relevance for the generation of immunological removal signals as biomarkers of old and/or damaged erythrocytes.