Condic M, Oberstein T, Herrmann M, Reimann MC, Kornhuber J, Maier JN, Spitzer P (2014)
Publication Type: Journal article
Publication year: 2014
Book Volume: 41
Pages Range: 116-25
DOI: 10.1016/j.bbi.2014.05.003
Abnormal accumulations of amyloid-? (A?)-peptides are one of the pathological hallmarks of Alzheimer's disease (AD). The precursor of the A?-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 A?-peptides during activation and phagocytosis, suggesting a physiologic role in inflammatory processes. Here, we show that supplementing the media with soluble N-terminally truncated A?(2-40) and A?(2-42) as well as A?(1-42) induced the phagocytosis of polystyrene particles (PSPs) by primary human monocytes. If the PSPs were pre-incubated with A?-peptides, phagocytosis was induced by all tested A?-peptide species. N-terminally truncated A?(x-42) induced the phagocytosis of PSPs significantly more effectively than did A?(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 A?(x-42). The proinflammatory polarization of monocytes was indicated by the reduced MSRI expression and IL-10 secretion after phagocytosis of PSPs coated with A?(1-42), A?(2-42) and A?(3p-42). Polarization of the macrophages by GM-CSF reduced the phagocytic activity, but it did not affect the capabilities of A?-peptides to opsonize prey. Taken together, A?-peptides support phagocytosis as soluble factors and act as opsonins. Differential effects among the A?-peptide variants point to distinct mechanisms of interaction among monocytes/macrophages, prey and A?-peptides. A proinflammatory polarization induced by the phagocytosis of A?-peptide coated particles may provide a model for the chronic inflammatory reaction and sustained plaque deposition in AD.
APA:
Condic, M., Oberstein, T., Herrmann, M., Reimann, M.C., Kornhuber, J., Maier, J.-N., & Spitzer, P. (2014). N-truncation and pyroglutaminylation enhances the opsonizing capacity of A?-peptides and facilitates phagocytosis by macrophages and microglia. Brain Behavior and Immunity, 41, 116-25. https://doi.org/10.1016/j.bbi.2014.05.003
MLA:
Condic, Mateja, et al. "N-truncation and pyroglutaminylation enhances the opsonizing capacity of A?-peptides and facilitates phagocytosis by macrophages and microglia." Brain Behavior and Immunity 41 (2014): 116-25.
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