Erythrocyte vesiculation: a self-protective mechanism?
ABSTRACT Previous studies demonstrated that 20% of haemoglobin is lost from circulating erythrocytes during their total lifespan by vesiculation. To study whether removal molecules other than membrane-bound haemoglobin were present in erythrocyte-derived vesicles, flow cytometry and immunoblot analysis were employed to examine the presence of phosphatidylserine (PS) and IgG, and senescent cell antigens respectively. It was demonstrated that 67% of glycophorin A-positive vesicles exposed PS, and that half of these vesicles also contained IgG. Immunoblot analysis revealed the presence of a breakdown product of band 3 that reacted with antibodies directed against senescent erythrocyte antigen-associated band 3 sequences. In contrast, only the oldest erythrocytes contained senescent cell antigens and IgG, and only 0.1% of erythrocytes, of all ages, exposed PS. It was concluded that vesiculation constitutes a mechanism for the removal of erythrocyte membrane patches containing removal molecules, thereby postponing the untimely elimination of otherwise healthy erythrocytes. Consequently, these same removal molecules mediate the rapid removal of erythrocyte-derived vesicles from the circulation.
Article: Storage-induced changes in erythrocyte membrane proteins promote recognition by autoantibodies.[show abstract] [hide abstract]
ABSTRACT: Physiological erythrocyte removal is associated with a selective increase in expression of neoantigens on erythrocytes and their vesicles, and subsequent autologous antibody binding and phagocytosis. Chronic erythrocyte transfusion often leads to immunization and the formation of alloantibodies and autoantibodies. We investigated whether erythrocyte storage leads to the increased expression of non-physiological antigens. Immunoprecipitations were performed with erythrocytes and vesicles from blood bank erythrocyte concentrates of increasing storage periods, using patient plasma containing erythrocyte autoantibodies. Immunoprecipitate composition was identified using proteomics. Patient plasma antibody binding increased with erythrocyte storage time, while the opposite was observed for healthy volunteer plasma, showing that pathology-associated antigenicity changes during erythrocyte storage. Several membrane proteins were identified as candidate antigens. The protein complexes that were precipitated by the patient antibodies in erythrocytes were different from the ones in the vesicles formed during erythrocyte storage, indicating that the storage-associated vesicles have a different immunization potential. Soluble immune mediators including complement factors were present in the patient plasma immunoprecipitates, but not in the allogeneic control immunoprecipitates. The results support the theory that disturbed erythrocyte aging during storage of erythrocyte concentrates contributes to transfusion-induced alloantibody and autoantibody formation.PLoS ONE 01/2012; 7(8):e42250. · 4.09 Impact Factor
Chapter: Phosphatidylserine Shedding from RBCs � A Mechanism of Membrane Modulation and Damage Control02/2012; , ISBN: 978-953-51-0138-3
Dataset: Clinical significance of circulating microparticles for venous thromboembolism in cancer patients[show abstract] [hide abstract]
ABSTRACT: Cancer patients have a four-to seven-fold in-creased risk to develop a venous thrombo -embolic event. Accumulating evidence from experimental and clinical studies indicates that microparticles (MPs), small procoagulant membrane vesicles that are defined by size and a negatively charged phosphatidylserine rich surface, play an important role in the pa-thogenesis of cancer-related venous throm-boembolism (VTE). However, the clinical sig-nificance of MPs as a predictive biomarker for VTE in cancer patients has not been fully eluci-dated yet. This might be due to unresolved methodological problems and a lack of data from large prospective clinical studies that in-vestigate the role of MPs in cancer-related VTE. It is the aim of this review to give an overview on the most important characteristics of MPs and studies dealing with the role of MPs in cancer-related VTE. Also recent progresses, unresolved problems and future perspectives in this research field will be discussed. In the conclusion we will assess the clinical signifi-cance of MPs in cancer-related VTE.