Hebestreit H Dibbert B Balatti I Braun D Schapowal A Blaser K Simon HU 1998 It has been suggested that Fas ligand-Fas receptor interactions are involved in the regulation of eosinophil apoptosis and that dysfunctions in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases. Here, we demonstrate that nitric oxide (NO) specifically prevents Fas receptor-mediated apoptosis in freshly isolated human eosinophils. In contrast, rapid acceleration of eosinophil apoptosis by activation of the Fas receptor occurs in the presence of eosinophil hematopoietins. Analysis of the intracellular mechanisms revealed that NO disrupts Fas receptor-mediated signaling events at the level of, or proximal to, Jun kinase (JNK), but distal to sphingomyelinase (SMase) activation and ceramide generation. In addition, activation of SMase occurs downstream of an interleukin 1 converting enzyme-like (ICE-like) protease(s) that is not blocked by NO. However, NO prevents activation of a protease that targets lamin B1. These findings suggest a role for an additional NO-sensitive apoptotic signaling pathway that amplifies the proteolytic cascade initialized by activation of the Fas receptor. Therefore, NO concentrations within allergic inflammatory sites may be important in determining whether an eosinophil survives or undergoes apoptosis upon Fas ligand stimulation. application/pdf https://sonar.ch/global/documents/22850 eng info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.187.3.415 info:eu-repo/semantics/altIdentifier/pmid/9449721 info:eu-repo/semantics/openAccess The Journal of experimental medicine. - 1998 Apoptosis Cell Survival Coculture Techniques Eosinophils Fas Ligand Protein Flow Cytometry Gene Expression Regulation, Neoplastic Histocytochemistry Humans Immunoblotting Membrane Glycoproteins Nasal Polyps Nitric Oxide Nitric Oxide Synthase RNA Second Messenger Systems Signal Transduction Tumor Cells, Cultured Disruption of fas receptor signaling by nitric oxide in eosinophils. http://purl.org/coar/resource_type/c_6501