Blocking of FcR Suppresses the Intestinal Invasion of Scrapie Agents

Prion diseases are a family of neurodegenerative zoonotic foodborne disorders. Although prions can be transmitted orally, the mechanism by which prions are incorporated into the intestine remains unclear. Our previous studies have shown that an abnormal isoform of prion protein (PrPSc), which is the main component of prions, was efficiently incorporated into the intestine in suckling mice but not in weaned mice. Furthermore, suckling SCID mice lacking maternal antibodies showed decreased uptake of PrPSc into the intestine compared with suckling wild-type mice, while the lack of PrPSc uptake into the intestine of suckling SCID mice was rescued by the oral administration of IgG. These findings raise the possibility that the neonatal Fc receptor (nFcR), which contributes to the uptake of maternal antibodies into the intestine, plays a role in PrPSc incorporation into the intestine. The present immunohistochemical study further showed that the FcR blocker Z-ε-aminocaproic acid (ZAA) inhibited PrPSc incorporation into the intestinal villi of suckling mice, supporting the above mentioned concept. Therefore, our findings provide strong evidence that nFcR and maternal antibodies are involved in PrPSc incorporation into the intestine before the weaning period

Structure of Z-ε-aminocaproic acid (ZAA).

<p>Z-ε-aminocaproic acid is a derivative form of ε-aminocaproic acid which is an analogue of the amino acid lysine.</p

Incorporation of IgG through the villi.

<p>Histochemical analysis of IgG in the intestinal villi of 15-day-old CD-1 mice that had been orally administered IgG (A: IgG), IgG after ZAA treatment (B: IgG after ZAA), or IgG and ZAA at the same time (C: IgG + ZAA). IgG was readily incorporated into the villi in A and partially incorporated in B and C. The number and percentage of ileal epithelial cells incorporating IgG were significantly higher in A than B and C. As a negative control, IgG was stained without exogenous IgG as D. The number of IgG-positive cells (E) and the ratio of IgG-positive cells (F) are expressed as the mean ± SD. The statistical significance of differences compared to oral administration of IgG was determined using One-way analysis of variance followed with Tukey's Multiple Comparison Test (Prism 4.03, GraphPad Software, Inc., La Jolla, CA, USA). **<i>p</i><0.01.</p

The inhibitory effect of ZAA on the incorporation of IgG and PrP^Sc on the basis of the ratio of IgG- or PrP^Sc-positive cells.

<p>The inhibitory effect of ZAA on the incorporation of IgG and PrP^Sc on the basis of the ratio of IgG- or PrP^Sc-positive cells.</p