Alzheimer's beta-amyloid peptide 1-42 induces a phagocytic response in murine microglia.
Beta-amyloid (A beta) peptides are a key component of the senile plaques that characterize Alzheimer's disease. Cytokine-producing microglia have been shown to be intimately associated with amyloid deposits and have also been implicated as scavengers responsible for clearing A beta deposits. However, little is known about the initial activation of these microglia or the effect of A beta on phagocytosis. Murine BV-2 microglia were used to assess the effect of synthetic A beta 1-42 on phagocytosis by quantifying uptake of fluorescent microspheres, acetylated low-density lipoproteins, and zymosan particles by flow cytometry. A beta 1-42 stimulated microglial phagocytosis in a time- and dose-dependent manner. A beta fibrils produced the greatest potentiation, and once activated, phagocytosis remained elevated after removal of A beta from the cultures. A beta-stimulated phagocytosis could be blocked if proteoglycans were first complexed to A beta fibrils. These data suggest that A beta fibrils act as an immune signal to stimulate microglial phagocytosis and that extracellular matrix molecules may modify A beta function.
Kopec
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Department of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Ann Arbor, Michigan 48105, USA.
Carroll
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RT
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D019812:Heparan Sulfate Proteoglycans / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010587:Phagocytosis / Q000502:physiology*; D013997:Time Factors; D015054:Zymosan / Q000378:metabolism
D016229:Amyloid beta-Peptides; D019812:Heparan Sulfate Proteoglycans; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D015054:Zymosan