Red blood cells, far more than oxygen transporters alone

In this thesis, we have gained insight into how red blood cells (RBCs) use the adhesion molecules they express, an aspect of RBC biology that has not been studied in great detail. First, we investigated the function of RBC adhesion molecules in immune adherence clearance, a process to protect the host from blood-borne infections. We have found evidence that RBCs adopt a “sticky” phenotype due to activation of the adhesion molecules ICAM-4 and CD147 after binding pathogens. Subsequently, we found that a filter can be used to clear RBC-pathogen complexes from blood due to this “sticky” phenotype. Based on this observation, we are currently developing a therapeutic approach to clear RBC-pathogen complexes from the blood of septic individuals. In addition, the function of the adhesion molecule Lu/BCAM, expressed on the RBC membrane was studied. Lu/BCAM is activated on sickle cell RBCs, leading to interaction with the extracellular matrix protein laminin-α5, contributing to vaso-occlusion and infarction of the spleen. RBCs from healthy individuals hardly adhere to laminin-α5. However, we found that aged RBCs do adhere via Lu/BCAM to laminin-α5 with similar rates as observed in sickle cells. We therefore hypothesized that activation of Lu/BCAM on aged RBCs could lead to trapping of these cells in the spleen. To address this, we analyzed the mechanism underlying Lu/BCAM-activation on ageing RBCs and assessed the interaction of these cells with laminin-α5. By means of these new insights we hope to be able to contribute to improved RBC-based therapies in the future.