Increased oxidative burst potential exhibited by macrophages during graft-versus-host reactions in mice

Graft versus host reactions (GVHR) in mice are accompanied by macrophage activation. Since macrophage oxidative burst (OB) was found to increase in activated macrophages (MPs), we examined the OB of peritoneal and spleen MPs from mice during GVHR. Parental spleen lymphocytes, were injected i.p. into F1 hybrids (BALB/cXC57Bl/6) and at different intervals following injection we monitored the number of peritoneal exudate cells (PEC), spleen enlargement, and the OB of both peritoneal and spleen adherent MPs. Macrophage OB was assessed by measuring O-2 and H2O2 production, following stimulation with the phorbol ester TPA. The spleen-to-body weight ratio increased by 40-70% in mice with GVHR during the period of 6-20 days post-injection and decreased to almost normal levels after 27 days. In such mice with GVHR the number of PEC returned to normal (approximately equal to 6 X 10(6) cells/animal) after 20 days compared with 5 days in control mice (injected with F1 spleen cells). Adherent peritoneal MPs from control mice and mice with GVHR exhibited increased OB activity 3 days following treatment. However, in the control mice the OB response returned to normal within 6 days, while in the experimental mice it showed a slight decrease after 6 days, increased again within 9-17 days, and finally decreased 20-27 days after treatment. Adherent spleen MPs from mice with GVHR generated a high response 6 days posttreatment, which gradually returned to the basal level after 17 days. These findings suggest that during GVHR in mice, macrophage OB was potentiated, giving rise to cytotoxic products such as O2- and H2O2, which may contribute to tissue damage during GVHR.