Interestingly, in Nc/Nga mice, total serum IgE levels were increasing between 7 and 14 days post infection with WR. We suggest that this IgE Noscapine hydrochloride increase in Nc/Nga mice might be due to constantly high amounts of mast cells in the skin of these mice that might lead to the release of mediators like heparin and histamin. Heparin can activate interferon-inducible dsRNA-activated protein kinase R, PKR, which is involved in IgE class switching and plays a role in IgE production. It was reported, that VACV inhibits PKR activation through the E3L protein, but in atopic Nc/Nga mice, this inhibition might be overcome by heparin; thus PKR can be still activated and contribute to IgE increase. Histological and immunohistochemical analyses further revealed the presence of chromatin debris at the sites of VACV inoculation, indicating a DNA fragmentation during the ongoing apoptosis. These results thus suggest that VACV inoculation into the skin might result in apoptosis rather than necrosis of infected cells. It has been previously established that VACV, typically considered as a lytic virus, causes apoptosis of various immune cell types. The type of cell death and presence of various PAMP��s and DAMP��s are critical for the type of immune SGI-1027 responses raised, and thus for better understanding to the postvaccination complications. It is therefore important to closely characterize the type of cell death induced by VACV in vivo in the individual cell types. The specific immunity of Nc/Nga, Balb/c and C57Bl/6 mice towards VACV strain WR was characterized by production of WR-specific IgG1 and IgG2a and by the capacity of mouse sera to neutralize the virus infectivity. The antibody responses were detectable only 14 days p.i. and they were relatively weak in all strains, as the peak levels are expected only later. Additionally, C57Bl/6 mice were reported to express the IgG2c isotype instead of IgG2a. On the other hand, neutralization tests indicated a clear difference between immune and nonimmune animals, with Nc/Nga mice revealing lower or delayed specific neutralization capacity than Balb/c mice.