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Originally published online as doi:10.1189/jlb.0906549 on December 8, 2006

Published online before print December 8, 2006
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(Journal of Leukocyte Biology. 2007;81:632-641.)
© 2007 by Society for Leukocyte Biology

Optimization of a myeloid cell transfusion strategy for infected neutropenic hosts

Brad J. Spellberg*,{dagger},1, Mary Collins*,2, Valentina Avanesian*, Mayela Gomez*,{ddagger}, John E. Edwards, Jr.*,{dagger}, Christopher Cogle§, David Applebaum||, Yue Fu*,{dagger} and Ashraf S. Ibrahim*,{dagger}

* Division of Infectious Diseases and
|| Department of Radiation Safety, Los Angeles Biomedical Research Institute, Harbor-University of California at Los Angeles Medical Center, and
{dagger} The David Geffen School of Medicine at UCLA, Torrance, California, USA;
{ddagger} California State University at Dominguez Hills, Carson, California, USA; and
§ University of Florida Shands Cancer Center, Gainesville, Florida, USA

1 Correspondence: Division of Infectious Diseases, Harbor-UCLA Medical Center, 1124 West Carson St., Torrance, CA 90502, USA. E-mail: bspellberg{at}labiomed.org

ABSTRACT

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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