Immunoreactivity for the Fas ligand in the mammalian enteric nervous system

The Fas ligand induces apoptosis in activated immunocytes that express the Fas receptor. Fas-ligand transcripts have been found previously in murine intestine but the intestinal tissues that express Fas ligand have not been identified. We used immunohistochemistry to examine the expression of the Fas ligand in the enteric nervous system of rats, mice, guinea-pigs, ferrets and humans. Fas-ligand immunoreactivity was detectable in enteric nerve fibres and neurons in all species tested, representing 25%-50% of the neurons in rats, mice and guinea-pigs. An antigen of approximately 48 kDa was detected by Western blot analysis with Fas-ligand antiserum in the dissected enteric plexuses of duodenum from a C3H/HeJ mouse. In gld mice that harbour a Fas-ligand mutation, Fas-ligand immunoreactivity was slightly more intense in neurons and fibres and was also apparent in submucosal lymphocytes. In the myenteric plexuses of guinea-pig ileum and human colon, Fas-ligand immunoreactivity was not contained in neurons exhibiting nicotinamide-adenine dinucleotide phosphate-diaphorase activity. In the submucosal plexus of guinea-pig ileum, labelled neurons included some neuropeptide-Y-containing neurons but none with vasoactive intestinal polypeptide. We conclude that the Fas ligand is expressed by a large subset of enteric neurons and may provide the basis for cytotoxic neuroimmune interactions in the intestines.