Our research focuses on the function, aging and clearance of red blood cells. In particular we have been investigating the role of CD47 on red cells in these processes. CD47 is an established ‘don’t eat me’ signal on red blood cells that prevents premature clearance by binding to the inhibitory immune receptor SIRPa on macrophages in the spleen and other relevant tissues. However, our findings suggest that CD47 does not only act as an inhibitory signal for phagocytosis, but may actually also promote phagocytosis directly by binding to SIRPa. Moreover, this role of CD47 as an ‘eat me’ signal appears most pronounced on aged red cells, suggesting that CD47 acts as a molecular switch from anti- to pro-phagocytic regulation. In addition, it seems that CD47 is somehow involved in red cell vesiculation, a specialized process aimed to shed red cell material that has become damaged, mostly as a result of oxidation, during the long life span of red cells. While the mechanistic basis for these phenomena is under further investigation these findings suggests that CD47-SIRPalpha interactions act as a critical regulator of erythrocyte survival and clearance, and therefore play a major role in red cell homeostasis.
In addition to this we are exploring a role of red cells as carriers of pathogens during bacterial infection. We have already observed that red cells can interact with opsonized bacteria and this is proposed to facilitate transport to and clearance by phagocytes present in the spleen and other tissues. This may also be of relevance in the context of sepsis, where erythrocyte transfusion may cause a relatively high frequency of transfusion-related acute lung injury (TRALI). The latter is being investigated in collaboration with dr Nicole Juffermans (Academic Medical Center).
- Burger P, Korsten H, de Korte D, Rombout E, van Bruggen R, Verhoeven AJ. An improved red blood cell additive solution maintains 2,3-diphosphoglycerate and adenosine triphosphate levels by an enhancing effect on phosphofructokinase activity during cold storage. Transfusion 2010; 50:2386-92.