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Infect Immun, June 1998, p. 2750-2754, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Augmentation of Human Macrophage Candidacidal Capacity by Recombinant Human Myeloperoxidase and GranulocyteMacrophage Colony-Stimulating Factor

László Maródi,1,* Christophe Tournay,2 Rita Káposzta,1 Richard B. Johnston Jr.,3 and Nicole Moguilevsky2

Department of Pediatrics, University School of Medicine, Debrecen, Hungary1; Department of Applied Genetics, Free University of Brussels, Nivelles, Belgium2; and Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut3

Received 18 December 1997/Returned for modification 2 February 1998/Accepted 24 March 1998

Phagocyte myeloperoxidase (MPO) is believed to be particularly important in defense against candida infection. We reported earlier that monocytes, rich in MPO, killed Candida albicans at a significantly higher rate and extent than did monocyte-derived macrophages, known to lack MPO, and that C. albicans is less resistant to MPO-dependent oxidants than less pathogenic Candida species. We hypothesized, therefore, that the capacity of macrophages to kill C. albicans might be improved in the presence of MPO. In this study, we evaluated the ability of recombinant human MPO (rhMPO) to augment the killing of C. albicans by resident macrophages and macrophages activated by recombinant human granulocyte-macrophage colony-stimulating factor. Addition of rhMPO (concentration range, 0.8 to 6.4 U/ml) to suspensions of resident and activated macrophages and opsonized C. albicans resulted in concentration-dependent and significant increases in candida killing. This enhancement was particularly pronounced with activated macrophages, whether C. albicans 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 the candidacidal capacity of both resident and activated macrophages, with a more profound effect on activated cells. We suggest that rhMPO may be effective in the treatment of invasive candidiasis.

* Corresponding author. Mailing address: Department of Pediatrics, University School of Medicine, H-4012 Debrecen, POB 32, Hungary. Phone: (36) (52) 430 323. Fax: (36) (52) 430 323. E-mail: marodi{at}gyermek.dote.hu.

Infect Immun, June 1998, p. 2750-2754, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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