Effect of pertussis toxin on the induction of nitric oxide synthesis in murine macrophages and on protection in vivo.

Macrophages from mice immunised with whole cell pertussis vaccine (WCV) responded in vitro to selected antigens by nitric oxide (NO) synthesis. This process was closely associated with macrophage activation. Because of the postulated role of traces of pertussis toxin (PT) in the protective effects of WCV, native PT and a genetically detoxified PT (g-PT) in combination with either a heat-treated whole cell pertussis vaccine (dWCV) or a three component acellular vaccine (ACV), were examined for their effects on NO induction in murine macrophages. The protective effects of these two forms of PT were examined in parallel using the intracerebral (ic) and aerosol challenge routes. Cultures of macrophages from mice immunised with dWCV and ACV, PT or g-PT produced less NO than comparable cultures from mice vaccinated with WCV. However, vaccination with either dWCV or ACV in combination with PT but not with g-PT, induced a significant increase (126-157%) in NO production by cultured cells and was associated with increased protection against challenge by both the ic and aerosol routes. These data indicate that a low concentration of PT acting as a co-factor in combination with other Bordetella pertussis antigens, can potentiate the activation of macrophages and that this process plays a key role in protection against infection.