Reactive microglia/macrophages phagocytose amyloid precursor protein produced by neurons following neural damage.
Kainic acid lesions of rat striatum caused an elevation of amyloid precursor protein (APP) immunoreactivity in neurons and neurites, some of which were then phagocytosed by reactive microglia/macrophages. Immunoexpression of APP was observed in neurites and neurons 1 day after the kainic injection. Four days after lesioning, immunoreactivity was still concentrated in thick and distorted neurites, but it began to appear in microglia/macrophages and in the tissue matrix. The cells were identified as microglia/macrophages by the phenotypic markers Ia (OX6), leukocyte common antigen (OX1), C3bi receptor (OX42), and macrophage marker (ED1). They were negative for the astrocytic marker glial fibrillary acidic protein (GFAP). APP immunoreactivity in these phagocytic cells was most prominent between 1 week and 1 month postlesioning. No extracellular amyloid fibrils were detectable. These results suggest that APP production is rapidly upregulated in damaged neurons and accumulates in degenerating axons. However, phagocytosis of APP by reactive microglia/macrophages in this rat model does not result in production of Alzheimer type amyloid deposits.
Shigematsu
K
K
Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada.
McGeer
P L
PL
Walker
D G
DG
Ishii
T
T
McGeer
E G
EG
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000032:analysis; D001369:Axons / Q000276:immunology / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000139:chemically induced / Q000378:metabolism; D016501:Neurites / Q000276:immunology / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D010477:Perfusion; D010587:Phagocytosis / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D007608:Kainic Acid