Red cell interactions with amyloid-beta(1-40) fibrils in a murine model

• Published in: Neurobiology of disease 2005-06, Vol.19 (1-2), p.28-37
• Main Authors: Ravi, Luke B, Poosala, Suresh, Ahn, Dongchoon, Chrest, Francis J, Spangler, Edward L, Jayakumar, Rajadas, Nagababu, Enika, Mohanty, Joy G, Talan, Mark, Ingram, Donald K, Rifkind, Joseph M
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - pharmacology; Amyloid beta-Peptides - physiology; Animals; Erythrocytes - drug effects; Erythrocytes - physiology; Liver - drug effects; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Models, Animal; Peptide Fragments - pharmacology; Peptide Fragments - physiology; Protein Binding - drug effects; Protein Binding - physiology; Spleen - drug effects; Spleen - metabolism
• ISSN: 0969-9961
• DOI: 10.1016/j.nbd.2004.11.004

Vascular amyloidosis in Alzheimer's disease (AD) results in the exposure of red blood cells to beta-amyloid fibrils (A beta). The potential in vivo ramifications of this exposure have been investigated by injecting A beta(1-40) alone or A beta-bound mouse red blood cells into the circulation of C57BL/6 mice. Results indicate that when A beta(1-40) is injected alone, a transient uptake of the fibrils by red blood cells occurs in vivo. When A beta-bound red blood cells were injected, beta-amyloid is rapidly removed from these cells in vivo. Double-labeling experiments indicate that while some of the red blood cells bound to A beta(1-40) are removed from circulation, a major fraction of these cells remain in circulation even after A beta is removed. Immunohistochemistry of murine tissue samples obtained after sacrificing the animals suggests that within 1 h after injection of A beta(1-40) or A beta-bound red blood cells, A beta is found in spleen phagocytes and liver Kupffer cells. Heme staining further indicates that the binding of A beta(1-40) to red blood cells enhances red cell phagocytosis by the spleen.