Murine and Human Mononuclear Phagocytes

as determined by vital staining, uptake of 2-deoxyglucose, and survival and replication in human fibroblasts. They are, however, rapidly killed by the addition of H202 and iodide under conditions in which control organisms are unaffected. We have used EPO bound to T. gondii to explore the role of peroxidase in the toxoplasmacidal activity of mononuclear phagocytes. Resident mouse peritoneal macrophages lack a granule peroxidase and have a weak respiratory burst; toxoplasma survive and replicate within these cells. However, these cells acquire significant toxoplasmacidal activity, as assessed microscopically and by the inhibition of uracil uptake, when organisms are coated with EPO before ingestion, an effect which is decreased by the hemeprotein inhibitors, aminotriazole and azide. EPO on the surface of Toxoplasma does not increase their ingestion by macrophages or the associated respiratory burst. Monocytes from patients with hereditary myeloperoxidase deficiency have a significant toxoplasmacidal defect that is abolished when Portions of this work have been presented at the National Meeting of the American Federation for Clinical Research, San Francisco, April, 1981. Dr. Wilson is a John A. and George L. Hartford Fellow. Address reprint requests to Dr. Locksley, Department of Medicine, University of Washington, Seattle, WA 98195. Received for publication 28 August 1981 and in revised form 16 November 1981. EPO-coated organisms are used. In contrast, the toxoplasmacidal defect of monocytes from chronic granulomatous disease patients is unaffected by surfacebound EPO. In these studies, replication of surviving intracellular organisms varied inversely with the magnitude of the respiratory burst: replication was greatest in fibroblasts, slightly less in resident macrophages, and least in monocytes; it was significantly greater in chronic granulomotous disease than in normal or myeloperoxidase-deficient monocytes. These studies support a role for oxygen products and endogenous peroxidase in the optimal killing of T. gondii by monocytes and demonstrate that peroxidase-negative phagocytes can utilize peroxidase on the surface of ingested organisms to augment microbicidal activity.