Involvement of a heat-stable and heat-labile component of Bordetella pertussis in the depression of the murine hepatic mixed-function oxidase system

Abstract

Experiments were conducted to determine whether the decrease in ethylmorphine N-demethylase and aniline hydroxylase activities and in the levels of cytochrome P-450 observed after injection of Bordetella pertussis to mice was related to an activity of the well-characterized 80°-heatlabile bacterial component (HSF) which causes an increased sensitivity to histamine. Temporal studies over 10–15 days following B. pertussis inoculation of mice suggested a possible correlation between the development of histamine sensitivity and the decrease in both in vivo and in vitro activities of the hepatic mixed-function oxidase system. Treatment of mice with unheated or 56°-heated vaccine produced a decrease in microsomal drug-metabolizing enzyme activity and an increased sensitivity to histamine at both 24 hr and 5 days after injection. In contrast, mice injected with an 80°-heated vaccine did not show an increased sensitivity to histamine at either time point or a decrease in drug-metabolizing activity at 5 days. There was, however, a significant loss of microsomal enzyme activity determined at 24 hr post-injection of the 80°-heated vaccine. Injection of B. pertussis into a strain of mice insensitive to HSF activity was shown to produce a decrease in the drug-metabolizing activity at both 24 hr and 5 days without the concomitant increase in histamine sensitivity. On the other hand, injection of partially purified HSF into a susceptible strain of mice produced histamine sensitization without the loss of hepatic enzyme activity. These studies suggest that HSF per se is not the bacterial component responsible for the reduction in the hepatic microsomal enzyme activity. The results would indicate that two separate bacterial components may be involved. One is stable to heat of 80° and may cause the acute (24 hr) loss of activity. The second is labile to heat between 56 and 80° and may be responsible for the prolonged (5–10 days) loss of enzyme activity. The identity of the heat-labile component is unknown but the former, heat-stable component may be bacterial endotoxin. This conclusion is based on the similarity between the transient reduction in drug-metabolizing activity produced by injection of 500 μmg/kg of endotoxin and that produced by the 80°-heated vaccine.