While there is a growing consensus on the understanding that the immune system plays an important role in facilitating the spread of
prion infections from the periphery to the central nervous system, little is known about the key players in the first steps of the
infection and about the sites of the disease development. Owing to their subepithelial location and their migratory capacity, macrophages could be early targets for
prion transportation or propagation during the later stages of disease. In order to investigate the role of macrophages, we studied in vitro the effect of exposing primary peritoneal macrophages to a synthetic
peptide homologous to residues 106-126 of the human
prion protein (PrP),
PrP 106-126. As shown by MTT assay, macrophage viability treated with less than 50 microM
PrP 106-126 for 72 h was not inhibited but slightly stimulated
at 10 and 25 microM, while there was significant decrease when exposed to 100 microM
PrP 106-126 for 72 h. The expressions of PrP at
mRNA and
protein level were up-regulated following treatment with
PrP 106-126 for 72 h.
Cytokine TNF-alpha production were elevated by the
PrP peptide in a time-dependent manner, which demonstrated a proinflammatory response linked to the presence and progression of
prion disease took place in macrophages. These findings suggested that macrophages may play roles in the transportation and replication of the infectious agent.