title: Ex vivo effects of macrophage colony-stimulating factor on human monocyte activity against fungal and bacterial pathogens.
abstract: The ex vivo effects of macrophage colony-stimulating factor (M-CSF) on antifungal and antibacterial activities of human elutriated monocytes were studied. Cells were isolated prior to the initiation of therapy, on day 3 and at week 7, in six patients with an advanced malignancy receiving M-CSF in a phase I study. Superoxide anion production by monocytes in response to N-formyl methionyl leucyl phenylalanine was enhanced at day 3 of therapy (P = 0.011). In addition, at day 3, fungicidal activity against blastoconidia of Candida albicans was enhanced by M-CSF treatment (P = 0.026), whereas antifungal activity against hyphae of Aspergillus fumigatus was not significantly changed. Bactericidal activity against Staphylococcus aureus was increased at day 3 (P = 0.004). By Northern blot analysis, M-CSF does not upregulate the expression of components of the NADPH-oxidase, the multicomponent enzyme system responsible for generation of superoxide radicals by monocytes. Instead, the predominant effect of M-CSF on circulating monocytes is probably a post-transcriptional effect. In conclusion, these findings suggest that administration of M-CSF to patients may enhance microbicidal activities and thus may provide a useful adjunct to conventional antimicrobial therapy.
authors: Infectious Diseases Section, National Cancer Institute, Bethesda, MD, USA.
authors: E
authors: E
authors: Roilides
authors: C A
authors: CA
authors: Lyman
authors: S D
authors: SD
authors: Mertins
authors: D J
authors: DJ
authors: Cole
authors: D
authors: D
authors: Venzon
authors: P A
authors: PA
authors: Pizzo
authors: S J
authors: SJ
authors: Chanock
authors: T J
authors: TJ
authors: Walsh
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001232:Aspergillus fumigatus; D001770:Blood Bactericidal Activity; D015152:Blotting, Northern; D002176:Candida albicans; D002478:Cells, Cultured; D006801:Humans; D007937:Leukapheresis; D016173:Macrophage Colony-Stimulating Factor / Q000009:adverse effects* / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis / Q000097:blood; D019255:NADPH Oxidases; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D010587:Phagocytosis; D013211:Staphylococcus aureus; D013481:Superoxides / Q000097:blood*
chemical_list: D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016173:Macrophage Colony-Stimulating Factor; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases