Factors produced by activated macrophages reduce accumulation of Alzheimer's beta-amyloid protein in vascular smooth muscle cells.
Smooth muscle cells (SMCs) isolated from amyloid-angiopathy affected brain vessels accumulate intracellularly amyloid-beta peptide (A beta). Now we demonstrate that accumulation of A beta in SMCs can be reduced by factors secreted by macrophages - IL-1alpha, IL-6, TNF-alpha, TGF-beta1 or PGE2 - probably by stimulating the non-amyloidogenic processing of A beta precursor protein (PP). It is suggested that brain macrophages may regulate A betaPP/A beta metabolism under physiological conditions and prevent beta-amyloidosis. The disturbance of this regulatory function of brain macrophages may result in excessive production and accumulation of A beta.
Mazur-Kolecka
B
B
New York State Institute for Basic Research in Developmental Disabilities, Department of Pathological Neurobiology, Staten Island 10314, USA.
Frackowiak
J
J
Le Vine
H
H
Haske
T
T
Wisniewski
H M
HM
D016564:Amyloid beta-Protein Precursor / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D004285:Dogs; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha