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Published online before print December 8, 2006
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*Division of Infectious Diseases and ||Department of Radiation Safety, Los Angeles Biomedical Research Institute, Harbor-University of California at Los Angeles (UCLA) Medical Center, and
The David Geffen School of Medicine at UCLA, Torrance, California, USA;
California State University at Dominguez Hills, Carson, California, USA; and
University of Florida Shands Cancer Center, Gainesville, Florida, USA
@ To whom correspondence should be addressed. E-mail: bspellberg{at}labiomed.org.
| Abstract |
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Although granulocyte transfusion is a logical, therapeutic option for neutropenic patients with refractory infections, significant technical barriers have prevented its widespread use. A novel phagocyte transfusion strategy has been developed based on activation of a human myeloid cell line HL-60. To further define the potential for HL-60 cells to recapitulate white cell transfusions, a shortened duration of activation was evaluated, facile quality control markers were defined, and the impact of low-dose irradiation on cell function was determined. Three days of activation resulted in increased cell viability and in vitro candidacidal capacity but with slightly higher cell replication compared with 7 days of activation. Cell viability and several flow cytometric measurements were accurate, quality control markers for HL-60 activation. In combination with activation, low-dose irradiation abrogated replication while sparing the candidacidal effects of the HL-60 cells. Infusion of irradiated, activated HL-60 cells improved survival of neutropenic, candidemic mice significantly. In summary, activated, irradiated HL-60 cells are microbicidal, have virtually no replicative capacity, and are safe and effective at protecting neutropenic mice against an otherwise 100% fatal candidal infection. With continued development, this strategy to recapitulate neutrophil functions has the potential to serve as an effective alternative to granulocyte transfusions.
Key Words: phagocyte neutrophil Candida
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