Effect of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on polymorphonuclear neutrophils, monocytes or monocyte-derived macrophages combined with voriconazole against Cryptococcus neoformans

2002 ◽  
Vol 40 (1) ◽  
pp. 21-26 ◽  
Author(s):  
T. Chiller ◽  
K. Farrokhshad ◽  
E. Brummer ◽  
D. A. Stevens
1998 ◽  
Vol 42 (4) ◽  
pp. 907-910 ◽  
Author(s):  
Shefali Vora ◽  
Nayanatara Purimetla ◽  
Elmer Brummer ◽  
David A. Stevens

ABSTRACT The antifungal activity of voriconazole (VCZ) was tested againstCandida albicans in the absence or presence of polymorphonuclear neutrophils (PMN) or monocytes. In some experiments, VCZ was compared to fluconazole (FCZ). On a weight basis, VCZ was 10-fold more efficacious than FCZ against C. albicans Sh27. Against an FCZ-resistant isolate, VCZ at 1 μg/ml produced the same fungistasis as FCZ at 20 μg/ml. VCZ at 0.1 μg/ml collaborated with PMN for enhanced killing to the same extent as FCZ at 1.0 μg/ml. Granulocyte-colony-stimulating factor (G-CSF) enhanced the candidacidal activity of PMN, and it increased the collaboration of PMN with VCZ for killing. Granulocyte-macrophage (GM)-CSF also significantly enhanced both the killing by PMN and the collaboration of PMN with VCZ for killing. VCZ collaborated with monocytes for enhanced killing ofC. albicans Sh27, and GM-CSF increased this collaboration. Taken together, these data show that VCZ is more potent than FCZ against C. albicans isolates, alone and in collaboration with PMN or monocytes for enhanced killing. In addition, G-CSF- or GM-CSF-activated PMN and monocytes have enhanced collaboration with VCZ compared to that of unstimulated phagocytes with VCZ.


1995 ◽  
Vol 15 (10) ◽  
pp. 5499-5507 ◽  
Author(s):  
K Krishnaraju ◽  
H Q Nguyen ◽  
D A Liebermann ◽  
B Hoffman

Previously we have shown that the zinc finger transcription factor Egr-1 is essential for and restricts differentiation of hematopoietic cells along the macrophage lineage, raising the possibility that Egr-1 actually plays a deterministic role in governing the development of hematopoietic precursor cells along the monocytic lineage. To test this hypothesis, we have taken advantage of interleukin-3-dependent 32Dcl3 hematopoietic precursor cells which, in addition to undergoing granulocytic differentiation in response to granulocyte colony-stimulating factor, were found to be induced for limited proliferation, but not differentiation, by granulocyte-macrophage colony-stimulating factor. It was shown that ectopic expression of Egr-1 blocked granulocyte colony-stimulating factor-induced terminal granulocytic differentiation, consistent with previous findings. In addition, ectopic expression of Egr-1 endowed 32Dcl3 cells with ability to be induced by granulocyte-macrophage colony-stimulating factor for terminal differentiation exclusively along the macrophage lineage. Thus, evidence that Egr-1 potentiates terminal macrophage differentiation has been obtained, suggesting that Egr-1 plays a deterministic role in governing the development of hematopoietic cells along the macrophage lineage.


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