Biomaterial Database

Macrophage colony-stimulating factor (M-CSF) induction of enhanced anticryptococcal activity in human monocyte-derived macrophages: synergy with fluconazole for killing. 1995

F Nassar, and E Brummer, and D A Stevens

Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128-2699, USA.

Induction of enhanced anticryptococcal activity in human monocyte-derived macrophages (HMM) by macrophage colony-stimulating factor (M-CSF) and possible synergy with fluconazole (FCZ) for killing of Cryptococcus neoformans (CN) was studied. Fungistasis by HMM cultured in medium for 3, 5, or 7 days was minimal, 0-17%. The fungistasis of HMM cocultured with M-CSF at 1000, 5000, or 20,000 U/ml for 3, 5, or 7 days was increased significantly (P < 0.02) at all study times and by all concentrations. The optimal M-CSF concentration for HMM treatment for enhanced fungistasis was 5000 U/ml for Day 3 (84%), whereas 1000 U/ml was sufficient with more prolonged HMM culture and M-CSF treatment (Days 5-7). The enhancement by M-CSF was seen with four different donors and three patient isolates of CN. FCZ at 5 micrograms/ml was fungicidal, 28 +/- 17% (n = 8). Killing by FCZ was enhanced by HMM treated with M-CSF 5000 or 20,000 U/ml for 5 days compared to control HMM, 58% (P = 0.001) and 60% (P = 0.002) vs 48%, respectively. This was also seen with HMM cultured with 1000 U/ml M-CSF for 7 days (P < 0.05). M-CSF also induced in HMM enhancement of fungistasis by lower, fungistatic, concentrations of FCZ. These results demonstrate enhancement of anticryptococcal activity by HMM treated with M-CSF and synergy with FCZ for inhibition and killing. These findings may provide a rationale for combined treatment of FCZ and M-CSF against cryptococcosis.

UI	MeSH Term	Description	Entries
D008264	Macrophages	The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)	Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003453	Cryptococcosis	Fungal infection caused by genus CRYPTOCOCCUS.	C gattii Infection,C neoformans Infection,C. gattii Infection,C. neoformans Infection,Cryptococcus Infection,Cryptococcus Infections,Cryptococcus gattii Infection,Torulosis,Cryptococcus neoformans Infection,C gattii Infections,C neoformans Infections,C. gattii Infections,C. neoformans Infections,Cryptococcoses,Cryptococcus gattii Infections,Cryptococcus neoformans Infections,Infection, C gattii,Infection, C neoformans,Infection, C. gattii,Infection, C. neoformans,Infection, Cryptococcus,Infection, Cryptococcus gattii,Infection, Cryptococcus neoformans,Infections, C gattii,Infections, C. neoformans,Toruloses
D003454	Cryptococcus	A mitosporic Tremellales fungal genus whose species usually have a capsule and do not form pseudomycellium. Teleomorphs include Filobasidiella and Fidobasidium.	Torula
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D015725	Fluconazole	Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.	Apo-Fluconazole,Béagyne,Diflucan,Fluc Hexal,FlucoLich,Flucobeta,Fluconazol AL,Fluconazol AbZ,Fluconazol Stada,Fluconazol von ct,Fluconazol-Isis,Fluconazol-ratiopharm,Flunazul,Fungata,Lavisa,Loitin,Neofomiral,Oxifungol,Solacap,Triflucan,UK-49858,Zonal,Apo Fluconazole,Fluconazol Isis,Fluconazol ratiopharm,UK 49858,UK49858
D016186	Receptor, Macrophage Colony-Stimulating Factor	A receptor for MACROPHAGE COLONY-STIMULATING FACTOR encoded by the c-fms proto-oncogene (GENES, FMS). It contains an intrinsic protein-tyrosine kinase activity. When activated the receptor undergoes autophosphorylation, phosphorylation of down-stream signaling molecules and rapid down-regulation.	Antigens, CD115,CD115 Antigens,CSF-1 Receptor,M-CSF Receptor,Macrophage Colony-Stimulating Factor Receptor,Proto-Oncogene Protein fms,Receptor, CSF-1,c-fms Protein,fms Proto-Oncogene Protein,CD115 Antigen,M-CSF Receptors,Macrophage Colony-Stimulating Factor Receptors,Receptors, CSF-1,Receptors, M-CSF,Receptors, Macrophage Colony-Stimulating Factor,Antigen, CD115,CSF-1 Receptors,M CSF Receptor,Macrophage Colony Stimulating Factor Receptor,Macrophage Colony Stimulating Factor Receptors,Proto-Oncogene Protein, fms,Receptor, CSF 1,Receptor, M-CSF,Receptor, Macrophage Colony Stimulating Factor,Receptors, CSF 1,Receptors, M CSF,Receptors, Macrophage Colony Stimulating Factor,c fms Protein,fms Proto Oncogene Protein