Alternative functions for TRAIL receptors in eosinophils and neutrophils

Background: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL ) induces apoptosis in many tumour cells but only rarely in normal cells. T he receptors of TRAIL belong to the superfamily of tumour necrosis factor ( TNF)/nerve growth factor (NGF) receptors. Here we investigate TRAIL recepto r expression and function in eosinophils and neutrophils. Methods: Granulocytes were isolated from human blood and purified using sta ndard protocols. Receptor expression was analysed by reverse transcription (RT)-PCR and flow cytometry. Cell death was analysed by the ethidium bromid e exclusion test. Apoptosis was determined by analysing phosphatidyl serine (PS) surface exposure and morphological evaluation. Results: Freshly purified eosinophils and neutrophils expressed TRAIL-R1, T RAIL-R3, and TRAIL-R4, but not TRAIL-R2 surface proteins. Stimulation of eo sinophils with TRAIL resulted in either inhibition of apoptosis or no effec t, depending on the individual from whom the cells were isolated. In neutro phils, TRAIL stimulation did not influence apoptosis. In eosinophils and ne utrophils which showed no effect on TRAIL stimulation alone, TRAIL partiall y blocked cytokine-mediated antiapoptosis. Conclusions: Both eosinophils and neutrophils express functional TRAIL rece ptors on their surface. In contrast to tumour cells, TRAIL does not induce apoptosis in granulocytes but rather induces survival in eosinophils from a pproximately 50% of the donors. Alternatively, TRAIL may limit cytokine-med iated antiapoptosis under certain inflammatory conditions.