Nitric oxide induction in murine macrophages and spleen cells by whole-cell Bordetella pertussis vaccine.

Nitric oxide (NO) induction was studied in the peritoneal macrophages and spleen cells of female NIH mice immunised with whole cell Bordetella pertussis vaccines of moderate and high potency, respectively. Compared with controls receiving diluent only, the macrophages and spleen cells of the vaccinated mice developed high levels of reactive nitrogen intermediates from the third day after injection. The nitrite concentrations achieved maximum values at the 10th day, but significant levels persisted until the 25th day. Heat-killed B. pertussis cells were the most effective inducer of NO synthesis, followed by lipopolysaccharide and agglutinogens Fim 2 and 3. Pertussis toxoid, filamentous haemagglutinin and pertactin were poor inducers of NO synthesis. The specific nitric oxide synthase inhibitor, aminoguanidine, and anti-IFN-gamma antibody blocked formation of nitrite by the macrophages and spleen cells. The production of NO in response to in vitro culture with bacterial antigen was clearly associated with protective immunity in vivo as determined by i.c. challenge. These results suggest that reactive nitrogen intermediates play a role in the immune response induced by whole cell pertussis vaccines.