Antifungal activity of splenic, liver and pulmonary macrophages against Candida albicans and effects of macrophage colony-stimulating factor

In the present study, culture supernatants from larger granular lymphocytes (LGL) that were activated with Candida albicans antigens were shown to stimulate the ability of neutrophils to inhibit fungal growth. Identification of the activation factors showed that granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor, was involved. Human peripheral blood mononuclear cells were fractionated by Percoll density centrifugation and each subpopulation of cells was stimulated with C albicans yeast cells. GM-CSF was produced in those fractions enriched for LGL, but not T lymphocytes or adherent monocytes. Additionally, the phenotype of the GM-CSF-producing cell was found to be CD2+, CD16+, HLA-DR+, and negative for CD4, CD8, and CD15. Kinetic studies demonstrated that GM- CSF appeared in the supernatants within 2 days of culture and continued to be produced up to 7 days. Optimal stimulation of LGL was seen at a ratio of 3 heat-killed C albicans yeast cells per LGL. Thus, LGL play an important role in host defense against this opportunistic pathogen by producing cytokines, including GM-CSF, which in turn activates the fungicidal activity of neutrophils.

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

Infection and Immunity ◽

10.1128/iai.66.6.2750-2754.1998 ◽

1998 ◽

Vol 66 (6) ◽

pp. 2750-2754 ◽

Cited By ~ 32

Author(s):

László Maródi ◽

Christophe Tournay ◽

Rita Káposzta ◽

Richard B. Johnston ◽

Nicole Moguilevsky

Keyword(s):

Candida Albicans ◽

Invasive Candidiasis ◽

Mannose Receptor ◽

Human Macrophage ◽

Activated Macrophages ◽

Colony Stimulating Factor ◽

Macrophage Mannose Receptor ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

ABSTRACT 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 opsonizedC. albicans resulted in concentration-dependent and significant increases in candida killing. This enhancement was particularly pronounced with activated macrophages, whetherC. 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.

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Activity of Voriconazole Combined with Neutrophils or Monocytes against Aspergillus fumigatus: Effects of Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.9.2299 ◽

1998 ◽

Vol 42 (9) ◽

pp. 2299-2303 ◽

Cited By ~ 50

Author(s):

Shefali Vora ◽

Sharda Chauhan ◽

Elmer Brummer ◽

David A. Stevens

Keyword(s):

Antifungal Activity ◽

Aspergillus Fumigatus ◽

Amphotericin B ◽

Hyphal Growth ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

ABSTRACT Voriconazole (VCZ) was tested for antifungal activity againstAspergillus fumigatus hyphae alone or in combination with neutrophils or monocytes. Antifungal activity was measured as percent inhibition of hyphal growth in assays using the dye MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] or XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide]. With both assays, VCZ inhibited hyphal growth at concentrations of <1 μg/ml and was almost as active as amphotericin B. VCZ (0.6 μg/ml) was sporicidal, as was amphotericin B (0.4 μg/ml). With both the MTT and XTT assays, neutrophils alone inhibited hyphae; when combined with VCZ, there was additive activity. Both granulocyte colony-stimulating factor- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated polymorphonuclear neutrophils (PMN) had enhanced inhibition of hyphal growth. Moreover, such treatment of PMN also enhanced the collaboration of PMN with VCZ. Monocytes inhibited hyphal growth. When VCZ was combined with monocytes or monocytes were treated with GM-CSF, inhibition was significantly increased, to similar levels. However, the combination of VCZ with GM-CSF treatment of monocytes did not significantly increase the high-level inhibition by monocytes with either agent alone.

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