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 i n 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, mi ce, guinea-pigs, ferrets and humans. Fas-ligand immunoreactivity was d etectable in enteric nerve fibres and neurons in all species tested, r epresenting 25%-50% of the neurons in rats, mice and guinea-pigs. An a ntigen of approximately 48 kDa was detected by Western blot analysis w ith 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 myenter ic plexuses of guinea-pig ileum and human colon, Fas-ligand immunoreac tivity was not contained in neurons exhibiting nicotinamide-adenine di nucleotide phosphate-diaphorase activity. In the submucosal plexus of guinea-pig ileum, labelled neurons included some neuropeptide-Y-contai ning neurons but none with vasoactive intestinal polypeptide. We concl ude that the Fas ligand is expressed by a large subset of enteric neur ons and may provide the basis for cytotoxic neuroimmune interactions i n the intestines.