Natural resistance of mice to Salmonella typhimurium: bactericidal activity and chemiluminescence response of murine peritoneal macrophages.

The phagocytic capacity of peritoneal macrophages from resistant C3Hf mice and sensitive C57Bl/6 mice was studied in vitro using a virulent and an avirulent strain of Salmonella typhimurium. Virulent and avirulent 3H-labelled bacteria opsonized with normal mouse serum were killed to an equal extent (about 40%) by macrophages from C3Hf mice and C57Bl/6 mice within 5 min after contact. Killing of both bacterial strains by macrophages from C3Hf mice continued at a lower rate for the next 30 min until about 40% of the remaining bacteria were killed. In this later phase macrophages from C57Bl/6 mice killed avirulent S. typhimurium to an extent comparable with the killing by macrophages from C3Hf mice, whereas macrophages from C57Bl/6 mice were unable to kill virulent S. typhimurium. Cytochalasin B did not inhibit the rapid initial killing of bacteria opsonized with normal mouse serum, but completely inhibited the slower phase of killing. From these results it is concluded that the resistance of the mice to infection with S. typhimurium correlates with the bactericidal activity of their peritoneal macrophages, and that killing of the bacteria occurs in an early extracellular phase followed by an intracellular phase. It is only the latter phase which reflects the animal's resistance to infection. The chemiluminescence response to macrophages to opsonized live S. typhimurium was independent of the susceptibility of the mice from which the macrophages were taken. Cytochalasin B and 2-deoxy-D-glucose reduced the chemiluminescence generated by opsonized or non-opsonized S. typhimurium. Comparison of the kinetics as well as inhibition, by cytochalasin B and 2-deoxy-D-glucose, of chemiluminescence and killing of S. typhimurium showed that the killing reaction of the peritoneal macrophages was not related to their chemiluminescence response.