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.

Balance between IL‐3 and type Iinterferons and their interrelationship with FasL dictates lifespan and effector functions of human basophils

“…A previous report suggested that basophils from chronic myeloid leukemia (CML) patients but not from healthy donors are weakly responsive to TRAIL . Figure c shows that multivalent TRAIL (KillerTRAIL) enhanced apoptosis of normal human blood basophils with similar efficacy as IFN‐α but more rapidly, with a significant effect detectable already after 24 h. Similar to IFN‐α, addition of IL‐3 protected the cells from TRAIL‐induced apoptosis.…”

“…Neutrophils and eosinophils rapidly undergo apoptosis after cross-linking of Fas [42,43]. However, the recently reported pro-apoptotic effect of anti-Fas antibody on basophils was only moderate [16]. We therefore wondered whether this is due to suboptimal crosslinking of Fas by the agonistic antibody or to the more apoptosis resistant phenotype of basophils that is manifested by their comparably prolonged lifespan, as reported earlier [15].…”

“…However, in contrast to type I IFNs, FasL and TRAIL provoked apoptosis more rapidly within 24 h. IL-3 strongly inhibited apoptosis induced by all three ligands albeit to different degrees. Although not explicitly discussed in the study by F€ orster et al [16], IL-3 was always included in their culture medium, providing a possible explanation why TRAIL showed no pro-apoptotic effect. As basophils secret themselves IL-3 upon FceRI cross-linking [62], it will be interesting to evaluate whether and how efficient FceRI cross-linking affects IFN-a, TRAIL and/or FasL-mediated apoptosis.…”

Mast Cells, Basophils and Mucosal Immunity

“…IL-3 prevents basophil apoptosis by inducing the antiapoptotic molecule Pim-1 (Didichenko et al, 2008). Activation of the Fas-Fas ligand pathway induces basophil apoptosis (Matsumoto et al, 2008;Forster et al, 2013), but the TNF-related apoptosiinducing lignad TRAIL pathway may be more important for apoptosis of neoplastic basophils (Forster et al, 2013). Many other factors, including leptin, IL-18, IL-33, and IL-25 prolong basophil survival (Suzukawa et al, 2011;Kroeger et al, 2009;Wang et al, 2010), but in contrast to human mast cells, FcεRI cross-linking does not seem to prolong human basophil survival in vitro (Xiang et al, 2006).…”

The Evolution of Human Basophil Biology from Neglect towards Understanding of Their Immune Functions

“…In contrast, human basophils express the death receptors CD95, tumor necrosis factor-related apoptosis-inducing ligand receptors (TRAIL-R)1, and TRAIL-R2 and treatment with an anti-CD95 antibody significantly increased apoptosis in basophils [98, 138]. Glucocorticoids, too, were shown to induce apoptosis in basophils and this apoptotic effect is considered responsible for their anti-inflammatory properties [139].…”