Antifungal activity of elutriated human monocytes against Aspergillus fumigatus hyphae: enhancement by granulocyte-macrophage colony-stimulating factor and interferon-gamma.

Human monocytes are important effector cells in host defenses against Aspergillus hyphae, and as elutriated monocytes (EHM) they may be transfused in large quantities to leukopenic patients with invasive aspergillosis. The antifungal activity of EHM against Aspergillus hyphae was compared with that of polymorphonuclear leukocytes (PMNL). The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) on superoxide anion (O2-) release and on hyphal damage caused by EHM against unopsonized A. fumigatus hyphae was investigated. EHM had antihyphal activity comparable to that of PMNL. GM-CSF significantly augmented O2- release by EHM in response to PMA. Also, both GM-CSF and IFN-gamma significantly enhanced the antifungal activity of EHM compared with untreated controls. Thus, EHM have demonstrable antifungal activity against Aspergillus hyphae that may be increased by GM-CSF and IFN-gamma, suggesting their potential therapeutic role in immune reconstitution of effector cells.

[1]  H. Malech,et al.  In vivo interferon-gamma therapy augments the in vitro ability of chronic granulomatous disease neutrophils to damage Aspergillus hyphae. , 1991, The Journal of infectious diseases.

[2]  E. Read,et al.  Stimulatory effect of counterflow centrifugal elutriation in large‐scale separation of peripheral blood monocytes can be reversed by storing the cells at 37°c , 1991, Journal of clinical apheresis.

[3]  E. Brummer,et al.  Kinetics and requirements for activation of macrophages for fungicidal activity: effect of protein synthesis inhibitors and immunosuppressants on activation and fungicidal mechanism. , 1991, Cellular immunology.

[4]  S. Banks,et al.  Granulocyte-macrophage colony-stimulating factor augments human monocyte fungicidal activity for Candida albicans. , 1990, The Journal of infectious diseases.

[5]  S. Reed,et al.  Recombinant granulocyte/macrophage colony-stimulating factor activates macrophages to inhibit Trypanosoma cruzi and release hydrogen peroxide. Comparison with interferon gamma , 1987, The Journal of experimental medicine.

[6]  J. David,et al.  Recombinant human granulocyte/macrophage colony-stimulating factor activates intracellular killing of Leishmania donovani by human monocyte-derived macrophages , 1987, The Journal of experimental medicine.

[7]  C. Nathan,et al.  Administration of recombinant interferon gamma to cancer patients enhances monocyte secretion of hydrogen peroxide. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Levitz,et al.  A rapid colorimetric assay of fungal viability with the tetrazolium salt MTT. , 1985, The Journal of infectious diseases.

[9]  E. Brummer,et al.  Recombinant and natural gamma-interferon activation of macrophages in vitro: different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi , 1985, Infection and immunity.

[10]  C. Haudenschild,et al.  Mechanisms of destruction of Aspergillus fumigatus hyphae mediated by human monocytes. , 1983, The Journal of infectious diseases.

[11]  A. Schaffner,et al.  Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes. , 1982, The Journal of clinical investigation.

[12]  D. Danley,et al.  Stimulation of oxidative metabolism in murine polymorphonuclear leukocytes by unopsonized fungal cells: evidence for a mannose-specific mechanism. , 1981, Journal of immunology.

[13]  A. Fauci,et al.  An improved technique for the negative selection of large numbers of human lymphocytes and monocytes by counterflow centrifugation--elutriation. , 1980, Cellular immunology.

[14]  R. Krzesicki,et al.  Damage to hyphal forms of fungi by human leukocytes in vitro. A possible host defense mechanism in aspergillosis and mucormycosis. , 1978, The American journal of pathology.