Journal of Leukocyte Biology
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Published online before print April 27, 2005
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0205072

Received for publication February 4, 2005.
Revised April 1, 2005.
Accepted for publication April 5, 2005.

Article

A phagocytic cell line markedly improves survival of infected neutropenic mice

Brad J. Spellberg *{dagger}@, Mary Collins *, Samuel W. French {dagger}{ddagger}, John E. Edwards Jr. *{dagger}, Yue Fu *{dagger}, and Ashraf S. Ibrahim *{dagger}

*Division of Infectious Diseases and {ddagger}Department of Pathology, Harbor-University of California at Los Angeles Medical Center; and {dagger}The David Geffen School of Medicine at the University of California at Los Angeles

@ To whom correspondence should be addressed. E-mail: bspellberg{at}labiomed.org.


  Abstract

Disseminated candidiasis is a frequent infection in neutropenic patients, in whom it causes 50% mortality, despite antifungal therapy. As the duration of neutropenia is the strongest predictor of survival in neutropenic patients with invasive fungal infections, neutrophil transfusions are a logical, therapeutic option. However, significant technical barriers have prevented the clinical use of neutrophil transfusions. To overcome these barriers, we identified a human phagocytic cell line that could be administered to candidemic hosts in lieu of freshly harvested neutrophils. HL-60 cells killed Candida albicans in vitro. Activation of HL-60 cells with dimethyl sulfoxide and retinoic acid abrogated cells’ proliferation and augmented their killing of C. albicans. Administration of activated HL-60 cells to candidemic, neutropenic mice significantly improved survival (53% vs. 0%). Live HL-60 cells chemotaxed to sites of infection, phagocytized C. albicans, and reduced the fungal burden in key target organs. Although unactivated HL-60 cells also reduced tissue fungal burden in vivo, they did not improve survival as a result of their toxicity in infected mice. In contrast, no toxicity as a result of activated HL-60 cells was observed at up to 2 months of follow-up. To our knowledge, this is the first description of a cell line-based immunotherapy for an infectious disease. With further refinements, activated HL-60 cells have the potential to overcome the technical barriers to neutrophil transfusions.

Key Words: HL-60 • immunotherapy • Candida albicans • white cell transfusions






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Copyright © 2005 by the Society for Leukocyte Biology.