Induction of macrophage migration by neurotoxic prion protein fragment.
Prion diseases are characterized by accumulation of protease resistant isoforms of prion protein (PrP), and infiltration and activation of mononuclear phagocytes at the brain lesions. Interactions between prion proteins and immune cells during disease progression are still not very well understood. In the present study, multiwell chamber chemotaxis assay was carried out to assess the migratory response of macrophage cell line Ana-1 to a synthetic peptide homologous to residues 106-126 of the human prion protein. Specific protein kinase inhibitors were used to elucidate the signaling events underlying PrP106-126-induced macrophages migration, and a comparison with the signaling pattern of macrophage migration induced by substance P (SP) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), respectively, was carried out. The results showed that PrP106-126 had a potent chemotactic effect on murine macrophage cell line Ana-1; that multiple signaling pathways might be involved in the PrP106-126-induced macrophage migrations; and that PrP106-126-induced chemotactic activity was similar to that induced by SP. These findings provide new insights into the mechanisms underlying the interaction between PrP and macrophages.
Zhou
Haiyun
H
National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.
Zhou
Xiangmei
X
Kouadir
Mohammed
M
Zhang
Zhongqiu
Z
Yin
Xiaomin
X
Yang
Lifeng
L
Zhao
Deming
D
D000818:Animals; D002452:Cell Count / Q000379:methods; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011328:Prions / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126); D013373:Substance P; D009240:N-Formylmethionine Leucyl-Phenylalanine