Phagocytosis in vitro of polyethylene glycol-modified liposome-encapsulated hemoglobin by human peripheral blood monocytes plus macrophages through scavenger receptors

Liposome-encapsulated hemoglobin (LEH), a candidate for red blood cell subs titute, is cleared from circulation primarily by the phagocytic system, mos t likely after opsonization of the vesicles by immunoproteins, particularly complement components. Although modification of LEH by polyethylene glycol (PEG) derivatives prolongs its half-life by blocking the opsonization, the half-life is still short as compared with that of red blood cell component s. Therefore, this study was performed to elucidate the opsonin-independent mechanisms that regulate phagocytosis of Neo Red Cell (NRC), a PEG-modifie d LEH, in culture. PKH67 was used as a fluorescence marker, allowing the qu antitation of the phagocytosis of NRC by peripheral blood monocytes plus ma crophages. The phagocytosis of PKH67-labeled NRC was inhibited by the addit ion of an excess of unlabeled NRC, indicating that the phagocytosis of PKH6 7-labeled NRC is specific to NRC, but not to PKH67. The phagocytosis of NRC was blocked about 70% by anti-CD14, 60% by anti-CD36 and 30% by anti-CD51/ 61 (vitronectin receptor, alphav beta3). These results provided evidence of an opsonin-independent pathway for the phagocytosis of PEG-modified LEH. ( C) 2001 Elsevier Science Inc. All rights reserved.