Free radicals and detoxification enzymes of inflammatory peritoneal neutrophils and macrophages

In our study to elucidate the biochemical basis of macrophage activation, we noted a transient surge (within 24 h) in neutrophil number in the peritoneal cavity following the injection of thioglycollate. By day 2 the peritoneal cell population consisted predominantly of vacuolated macrophages. In order to understand the possible cause of the above short-lived increase in neutrophils, we compared the capacity to produce toxic free radicals (by measuring luminol-dependent chemiluminescence) and the activities of detoxification enzymes, namely, glutathione peroxidase and glutathione reductase, between neutrophils (day-1 cells) and the day-2 cells, which were predominantly macrophages. The results show that the neutrophils obtained 1 day after elicitation by thioglycollate produced an intense burst of luminol-dependent chemiluminescence, approximately 7-fold greater than that of the day-2 macrophages. This was true despite a markedly enhanced oxygen consumption by the latter compared with that by the neutrophils. In addition there were marked differences in the onset and duration of the response. Investigations on the activities of detoxification enzymes, especially glutathione peroxidase and glutathione reductase, which are known to be coupled to the oxidative segment of the pentose phosphate pathway, revealed neutrophils to have a reduced capacity to detoxify free radicals and peroxides in comparison with elicited macrophages. These findings suggest that the neutrophils, despite their enhanced capacity to emit toxic free radicals and peroxides, are less efficient in protecting themselves, which ultimately may cause cell death and, as a consequence, a decline in their cell. number at the site of inflammation.