AUGMENTATION OF HUMAN MACROPHAGE CANDIDACIDAL CAPACITY BY RECOMBINANTHUMAN MYELOPEROXIDASE AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

Phagocyte myeloperoxidase (MPO) is believed to be particularly importa nt in defense against candida infection. We reported earlier that mono cytes, rich in MPO, killed Candida albicans at a significantly higher rate and extent than did monocyte-derived macrophages, known to lack M PO, and that C. albicans is less resistant to MPO-dependent oxidants t han less pathogenic Candida species. We hypothesized, therefore, that the capacity of macrophages to kill C. albicans might be improved in t he presence of MPO. In this study, we evaluated the ability of recombi nant human MPO (rhMPO) to augment the killing of C. albicans by reside nt macrophages and macrophages activated by recombinant human granuloc yte-macrophage colony-stimulating factor. Addition of rhMPO (concentra tion range, 0.8 to 6.4 U/ml) to suspensions of resident and activated macrophages and opsonized C. albicans resulted in concentration-depend ent and significant increases in candida killing. This enhancement was particularly pronounced with activated macrophages, whether C. at alb icans was opsonized or unopsonized and ingested through the macrophage mannose receptor. rhMPO did not affect the killing of C. albicans by monocytes, nor did it affect phagocytosis of opsonized or unopsonized C. albicans. These results indicate that exogenous rhMPO can augment t he candidacidal capacity of both resident and activated macrophages, w ith a mori: profound effect on activated cells, We suggest that rhMPO may be effective in the treatment of invasive candidiasis.