Ex vivo effects of macrophage colony-stimulating factor on human monocyte activity against fungal and bacterial pathogens.
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.
Roilides
E
E
Infectious Diseases Section, National Cancer Institute, Bethesda, MD, USA.
Lyman
C A
CA
Mertins
S D
SD
Cole
D J
DJ
Venzon
D
D
Pizzo
P A
PA
Chanock
S J
SJ
Walsh
T J
TJ
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*
D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D016173:Macrophage Colony-Stimulating Factor; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases