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To identify uniquely expressed cytokine genes in human neutrophils and evaluate the cytotoxic antitumor potential of neutrophil-derived TRAIL.

February 1, 2004Cancer Research

Neutrophil-Derived TNF-Related Apoptosis-Inducing Ligand (TRAIL)

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To identify uniquely expressed cytokine genes in human neutrophils and evaluate the cytotoxic antitumor potential of neutrophil-derived TRAIL.
Screened cytokine gene expression profiles between healthy human donor neutrophils and PHA-stimulated PBMCs using a 240-cytokine cDNA microarray.
Quantified TRAIL mRNA and protein levels via real-time RT-PCR and ELISA under resting conditions and following IFN-γ stimulation.
Assayed cytotoxicity against Jurkat cells by flow cytometry using annexin V staining across varying effector-to-target ratios with and without neutralizing anti-TRAIL antibodies.
Identified 26 genes expressed >10 times higher in neutrophils than PBMCs, including TRAIL mRNA and protein, which upregulated significantly upon IFN-γ stimulation.
Observed surface expression and soluble release of TRAIL by neutrophils, which induced apoptosis in Jurkat cells in an effector:target ratio-dependent manner.
Demonstrated that the cytotoxic effect on Jurkat cells was partially suppressed upon addition of neutralizing anti-TRAIL antibody.

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In vitro study demonstrates functional TRAIL expression in human neutrophils, indicating a direct neutrophil-mediated antitumor cytotoxic mechanism.

Koga et al. (2004) studied this question.

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In vitro study demonstrates functional TRAIL expression in human neutrophils, indicating a direct neutrophil-mediated antitumor cytotoxic mechanism.