Red cell interactions with amyloid-beta(1-40) fibrils in a murine model.
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.
Ravi
Luke B
LB
Molecular Dynamics Section, Gerontology Research Center, National Institute on Aging (Fully accredited by the American Association for the Accreditation of Laboratory Animal Care.), 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Poosala
Suresh
S
Ahn
Dongchoon
D
Chrest
Francis J
FJ
Spangler
Edward L
EL
Jayakumar
Rajadas
R
Nagababu
Enika
E
Mohanty
Joy G
JG
Talan
Mark
M
Ingram
Donald K
DK
Rifkind
Joseph M
JM
D016229:Amyloid beta-Peptides / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010446:Peptide Fragments / Q000494:pharmacology / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)