N-truncation and pyroglutaminylation enhances the opsonizing capacity of Aβ-peptides and facilitates phagocytosis by macrophages and microglia
| Autor: | Juan Manuel Maler, Mareike Carola Reimann, Philipp Spitzer, Mateja Condic, Johannes Kornhuber, Martin Herrmann, Timo Jan Oberstein |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Swine
Macrophage Phagocytosis Immunology Sus scrofa Macrophage polarization Nitric Oxide Synthase Type II Biology Monocyte Monocytes Proinflammatory cytokine Cell Line Behavioral Neuroscience Structure-Activity Relationship Neuroinflammation Opsonization medicine Escherichia coli Animals Humans Opsonin Amyloid beta-Peptides Microglia Endocrine and Autonomic Systems Macrophage Colony-Stimulating Factor Macrophages Granulocyte-Macrophage Colony-Stimulating Factor Macrophage Activation Opsonin Proteins Aβ-peptides Microspheres Peptide Fragments Cell biology Interleukin-10 Protein Structure Tertiary Pyrrolidonecarboxylic Acid Antibody opsonization medicine.anatomical_structure Biochemistry Amyloid precursor protein Protein Processing Post-Translational |
| Zdroj: | Brain, Behavior, and Immunity. :116-125 |
| ISSN: | 0889-1591 |
| DOI: | 10.1016/j.bbi.2014.05.003 |
| Popis: | Abnormal accumulations of amyloid-β (Aβ)-peptides are one of the pathological hallmarks of Alzheimer’s disease (AD). The precursor of the Aβ-peptides, the amyloid precursor protein (APP), is also found in peripheral blood cells, but its function in these cells remains elusive. We previously observed that mononuclear phagocytes release Aβ-peptides during activation and phagocytosis, suggesting a physiologic role in inflammatory processes. Here, we show that supplementing the media with soluble N-terminally truncated Aβ(2–40) and Aβ(2–42) as well as Aβ(1–42) induced the phagocytosis of polystyrene particles (PSPs) by primary human monocytes. If the PSPs were pre-incubated with Aβ-peptides, phagocytosis was induced by all tested Aβ-peptide species. N-terminally truncated Aβ(x–42) induced the phagocytosis of PSPs significantly more effectively than did Aβ(x–40). Similarly, the phagocytosis of Escherichia coli by GM-CSF- and M-CSF-elicited macrophages as well as microglia was particularly facilitated by pre-incubation with N-terminally truncated Aβ(x–42). The proinflammatory polarization of monocytes was indicated by the reduced MSRI expression and IL-10 secretion after phagocytosis of PSPs coated with Aβ(1–42), Aβ(2–42) and Aβ(3p–42). Polarization of the macrophages by GM-CSF reduced the phagocytic activity, but it did not affect the capabilities of Aβ-peptides to opsonize prey. Taken together, Aβ-peptides support phagocytosis as soluble factors and act as opsonins. Differential effects among the Aβ-peptide variants point to distinct mechanisms of interaction among monocytes/macrophages, prey and Aβ-peptides. A proinflammatory polarization induced by the phagocytosis of Aβ-peptide coated particles may provide a model for the chronic inflammatory reaction and sustained plaque deposition in AD. |
| Databáze: | OpenAIRE |
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