Optimization of a myeloid cell transfusion strategy for infected neutropenic hosts.
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.
Spellberg
Brad J
BJ
Division of Infectious Diseases, Harbor-UCLA Medical Center, Torrance, CA 90502, USA. bspellberg@labiomed.org
Collins
Mary
M
Avanesian
Valentina
V
Gomez
Mayela
M
Edwards
John E
JE
Cogle
Christopher
C
Applebaum
David
D
Fu
Yue
Y
Ibrahim
Ashraf S
AS
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000276:immunology* / Q000628:therapy; D002470:Cell Survival / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D017708:Leukocyte Transfusion / Q000379:methods; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D022423:Myeloid Cells / Q000276:immunology* / Q000528:radiation effects / Q000637:transplantation*; D009503:Neutropenia / Q000276:immunology / Q000628:therapy*; D014183:Transplantation, Heterologous