Oligomeric amyloid-beta(1-42) induces THP-1 human monocyte adhesion and maturation.
Amyloid-beta (Abeta) is a naturally occurring 40- or 42-residue peptide fragment with a primary role in Alzheimer's disease (AD). Aggregated Abeta accumulates as both dense core plaques and diffuse deposits in the brains of AD patients. Abeta plaques are surrounded by activated microglia, some of which are believed to be derived from peripheral blood monocytes that have infiltrated the central nervous system and differentiated into phagocytes in response to Abeta. We have modeled this process using THP-1 human monocytes and found Abeta(1-42) to be as effective as phorbol myristate acetate at differentiating THP-1 monocytes based on cell adhesion, fibronectin binding, CD11b cell-surface expression, and morphological changes. Cell adhesion studies and atomic force microscopy imaging revealed an inverse correlation between Abeta(1-42)-induced monocyte maturation and aggregation progression. Freshly reconstituted Abeta(1-42) solutions were the most effective, yet continued aggregation reduced, and eventually abolished, the ability to induce monocyte adhesion. Abeta(1-40), lower aggregation concentrations of Abeta(1-42), and an aggregation-restricted Abeta(1-42) L34P mutant had little effect on monocyte adhesion under the same conditions as Abeta(1-42). These findings implicated an oligomeric, but not monomeric or fibrillar, Abeta(1-42) aggregation species in the monocyte maturation process. The rapidly-formed Abeta(1-42) oligomers were distinct from Abeta-derived diffusible ligands which did not elicit significant THP-1 monocyte adhesion. These data demonstrate that a specific oligomeric Abeta(1-42) aggregation species can potently initiate the THP-1 monocyte maturation process.
Crouse
Nikkilina R
NR
Department of Chemistry and Biochemistry and Center for Nanoscience, University of Missouri-St. Louis, One University Boulevard, St. Louis, MO 63121, USA.
Ajit
Deepa
D
Udan
Maria L D
ML
Nichols
Michael R
MR
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D039481:CD11b Antigen; D005353:Fibronectins; C509295:ITGAM protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C016658:phorbolol myristate acetate; D013755:Tetradecanoylphorbol Acetate