Polyethylenimine-Induced Alterations of Red Blood Cells and Their Recognition by the Complement System and Macrophages

In practical applications, biomedical materials introduced in vivo may interact with various host cells and/or biomacromolecules and alter their physiological characteristics. Biomaterial-altered cells and/or biomacromolecules may be recognized as "non-self" by the host immune system and may consequently cause further immune responses. In the present work, the gene carrier material branched polyethylenimine (1.8 kDa) (BPEI-1.8k) induced a series of alterations of human red blood cells (RBCs), such as a morphological transition from biconcave disks to spheroechinocytes, vesiculation, a size decrease, a change in surface charge from negative to positive, a cell density reduction, membrane oxidation, and PS externalization. Furthermore, BPEI-1.8k-treated RBCs caused autologous complement activation and were recognized by autologous macrophages. This implies that the biomedical material BPEI-1.8k changed the identity of the RBCs, leading to their recognition by the autologous immune system. This study provides novel insights for the biocompatibility evaluation and clinical application of biomedical materials.