The amino-terminus of the amyloid-beta protein is critical for the cellular binding and consequent activation of the respiratory burst of human macrophages.
Here, we show that amyloid-beta (Abeta) is capable to prime and activate the respiratory burst of human macrophages. Previously, the N-terminus of Abeta(1-42) has been shown to contain a cell binding domain that is implicated in eliciting neuropathogenic microglia in vitro. To evaluate the role of this domain in the Abeta(1-42)-induced respiratory burst activity, the effect of Abeta subfragments on the Abeta(1-42)-induced superoxide release were studied. On the basis of the antagonistic properties of Abeta(1-16), it is concluded that the N-terminal region of Abeta is critical for the cellular binding and consequent activation of the respiratory burst of human phagocytes.
Van Muiswinkel
F L
FL
Graduate School Neurosciences Amsterdam, Research Institute Neurosciences, Vrije Universiteit, Faculty of Medicine, Department of Pharmacology, The Netherlands. flv.muiswinkel.pharm@med.vu.nl
Raupp
S F
SF
de Vos
N M
NM
Smits
H A
HA
Verhoef
J
J
Eikelenboom
P
P
Nottet
H S
HS
D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects / Q000276:immunology; D001923:Brain Chemistry / Q000276:immunology; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D008163:Luminescent Measurements; D008264:Macrophages / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D009000:Monocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding / Q000276:immunology; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism
D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D010446:Peptide Fragments; C115195:amyloid beta-protein (1-11); C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D013481:Superoxides; D016650:Fluorescein-5-isothiocyanate