Adherence-dependent shifts in the patterns of β-amyloid peptides secreted by human mononuclear phagocytes

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• 作者：Juan Manuel Maler ; Philipp Spitzer ; Hans-Wolfgang Klafki ; Hermann Esselmann ; Mirko Bibl ; Piotr Lewczuk ; Johannes Kornhuber ; Martin Herrmann ; Jens Wiltfang
• 关键词：β ; -Amyloid ; Monocytes ; Mononuclear phagocytes ; Dementia ; Alzheimer disease ; Neuroinflammation ; Biological markers
• 刊名：Brain, Behavior, and Immunity
• 出版年：2008
• 出版时间：October 2008
• 年：2008
• 卷：22
• 期：7
• 页码：1044-1048
• 全文大小：441 K

文摘

Cells of the mononuclear phagocyte system are closely associated with vascular and neuritic β-amyloid deposits in Alzheimer’s disease. Using one-dimensional and newly developed two-dimensional Aβ-SDS–PAGE Western immunoblot techniques (1D/2D-Aβ-WIB) we investigated the patterns of Aβ peptides released by primary non-adherent and adherence-activated human mononuclear phagocytes in vitro. An overall increase of total released Aβ peptides (Aβ_total) was observed in adherence-activated mononuclear phagocyte cultures. 2D-Aβ-WIB revealed that the proportion of Aβ_1–40 decreased significantly to 50.2 ± 5.4 % (n = 10) of Aβ_total compared to 65.9 ± 5.6 % (n = 7) in non-adherent cultures (p < 0.0001, t = 5.82). Aβ_1–42 accounted for only 3.0 ± 2.1 % of Aβ_total and its proportion did not change significantly upon adherence (2.8 ± 0.5 % of Aβ_total). In adherence-activated cultures we detected pronounced shifts in the fractional pattern of released Aβ peptides in favour of N-truncated species. The second most prominent Aβ peptide accounted for as much as 12.7 ± 3.0 % of Aβ_total (2.0 ± 1.2 % in non-adherent cultures; p < 0.0001, t = 9.00) and was identified as Aβ_2–40 by comigration with a synthetic peptide and by N-terminal-specific antibodies. A strong increase of a further Aβ immunoreactive spot migrating at pI 5.45 was observed. It accounted for 9.2 ± 1.7 % of Aβ_total as compared to 1.0 ± 0.9 % in non-adherent cultures (p < 0.0001, t = 11.61) and presumably represented a variant of Aβ_2–40 as determined by C-terminal Aβ₄₀-specific immunoprecipitation and N-terminal-specific immunodetection. Thus, mononuclear phagocytes might be one source of the N-truncated Aβ peptides regularly found in human plasma and are less likely to contribute substantially to plasma Aβ_1-42.