Phagocytosis and killing of Salmonella by 7-hydroxycoumarin activated macrophages.

Coumarin and its derivatives have potent immunomodulatory activities. Here we describe the parameters of the protective effect of 7-hydroxycoumarin (7-OHC) in experimental Salmonella enterica Serovar Typhimurium infection in mice. The protective effect depended on the duration of treatment reaching its maximum after 10 days of pretreatment and lasted for at least 15 days after its end. Electron microscopy studies revealed that 7-OHC induced ultrastructural changes in macrophages consistent with their activation as well as faster destruction of ingested salmonellae. Superoxide and hydrogen peroxide secretion by macrophages was decreased in both healthy and Salmonella-infected 7-OHC treated animals, which is in line with the current view that some coumarins possess antioxidant and radical scavenging activity. Thus, 7-OHC pretreatment also appears beneficial to the host by limiting the harmful tissue damaging and immunosuppressive effects of the oxidative stress during a Salmonella infection but still activates the microbicidal capacity of exposed phagocytes.