Fibrillar prion peptide (106-126) and scrapie prion protein hamper phagocytosis in microglia.
The inflammatory response in prion diseases is dominated by microglial activation. As macrophages of the central nervous system, the phagocytic capacity of microglia is well recognized, and it is possible that microglia are involved in the removal and processing of amyloid fibrils, thus preventing their harmful effect. We have analyzed the effects of a synthetic peptide of the human prion protein, PrP(106-126), which can form fibrils, and the pathogenic form of prion protein, PrPsc, on phagocytosis in microglia isolated from neonatal rat brain cultures. To some extent, fibrillar PrP(106-126) is internalized and processed. However, both synthetic prion peptide PrP(106-126) in a fibrillar form and pathogenic prion protein PrPsc severely hamper the phagocytic activity as measured by the uptake of beads by microglia. At a concentration that does not induce microglial death, PrP(106-126) reduced the number of beads internalized and altered their cytoplasmic distribution. This effect was not due to decreased binding of beads to the cell surface, nor restricted to specific classes of receptors. Although the PrP(106-126) did not prevent F-actin and Rac1 accumulation at sites of particle engulfment, it appeared to interfere with a later step of the internalization process.
Ciesielski-Treska
Jaroslava
J
CNRS UPR-2356 Neurotransmission et Sécrétion Neuroendocrine, IFR 37 des Neurosciences Centre de Neurochimie, Strasbourg, France. ciesielski-treska@neurochem.u-strasbg.fr
Grant
Nancy J
NJ
Ulrich
Gabrielle
G
Corrotte
Matthias
M
Bailly
Yannick
Y
Haeberle
Anne-Marie
AM
Chasserot-Golaz
Sylvette
S
Bader
Marie-France
MF
D000199:Actins / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D018620:PrPSc Proteins / Q000494:pharmacology*; D011328:Prions / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D000906:Antibodies; D010446:Peptide Fragments; D018620:PrPSc Proteins; D011328:Prions; C082632:prion protein (106-126); D020830:rac1 GTP-Binding Protein