Anti-Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) differentially regulate apoptosis in normal and neoplastic human basophils

Abstract

Basophilia is associated with allergic and parasitic diseases and advanced chronic myeloid leukemia. In the present study, we characterized the expression and function of the death receptors Fas/CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors in basophils from healthy donors compared to neoplastic basophils. Peripheral blood basophils obtained from healthy donors (HD-PBB) and from patients with chronic myeloid leukemia (CML-PBB) were found to express high levels of Fas/CD95 and low levels of TRAIL-R2, whereas the basophil-like chronic myeloid leukemia cell line KU-812 expressed significant levels of TRAIL-R1 and TRAIL-R2. HD-PBB underwent apoptosis in response to anti-Fas/CD95, but showed resistance to TRAIL, unless they were co-treated with actinomycin D. Interestingly, CML-PBB and KU-812 cells exhibited the opposite response pattern with resistance to anti-Fas/CD95, but significant susceptibility to TRAIL-induced apoptosis. Our data show that anti-Fas/CD95 and TRAIL differentially regulate apoptosis of normal and neoplastic human basophils, which may direct the development of novel therapeutic strategies.

Keywords::

• Apoptosis
• basophils
• CD95
• chronic myeloid leukemia
• TRAIL

Acknowledgements

The authors thank C. Berns, Department of Dermatology, University of Cologne, for excellent technical assistance, and Adriano G. Rossi, Centre for Inflammation Research, University of Edinburgh, for hosting K.P. for some experiments. They would also like to acknowledge the BMBS COST Action BM1007 “Mast Cells and Basophils – Targets for Innovative Therapies,” which facilitated their collaboration on this study.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This study was supported by research grants from the German Research Council (DFG; grant CRC/SFB832, project A14), the German-Israeli Foundation for Scientific Research and Development (993/2008) and the Wilhelm Sander Foundation (1999.049.2) to K.H., and by a research grant from the Austrian Science Fund (FWF; SFB grant # F4611-B19) to P.V. L.M.P. and B.S.F. were supported by the Koeln Fortune Program, Faculty of Medicine, University of Cologne (18/1999, 124/2000).