Alternative functions for TRAIL receptors in eosinophils and neutrophils

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many tumour cells but only rarely in normal cells. The receptors of TRAIL belong to the superfamily of tumour necrosis factor (TNF)/nerve growth factor (NGF) receptors. Here we investigate TRAIL receptor expression and function in eosinophils and neutrophils.

Granulocytes were isolated from human blood and purified using standard protocols. Receptor expression was analysed by reverse transcription (RT)-PCR and flow cytometry. Cell death was analysed by the ethidium bromide exclusion test. Apoptosis was determined by analysing phosphatidyl serine (PS) surface exposure and morphological evaluation.

Freshly purified eosinophils and neutrophils expressed TRAIL-R1, TRAIL-R3, and TRAIL-R4, but not TRAIL-R2 surface proteins. Stimulation of eosinophils with TRAIL resulted in either inhibition of apoptosis or no effect, depending on the individual from whom the cells were isolated. In neutrophils, TRAIL stimulation did not influence apoptosis. In eosinophils and neutrophils which showed no effect on TRAIL stimulation alone, TRAIL partially blocked cytokine-mediated antiapoptosis.

Both eosinophils and neutrophils express functional TRAIL receptors on their surface. In contrast to tumour cells, TRAIL does not induce apoptosis in granulocytes but rather induces survival in eosinophils from approximately 50% of the donors. Alternatively, TRAIL may limit cytokine-mediated antiapoptosis under certain inflammatory conditions.