Multiple mechanisms contribute to myenteric plexus ablation induced by benzalkonium chloride in the guinea-pig ileum

• Published in: Cell and tissue research Vol. 289; no. 2; pp. 253 - 264
• Main Authors: Parr, E J, Sharkey, K A
• Format: Journal Article
• Language: English
• Published: Germany 01.08.1997
• Subjects: AIDS/HIV; Animals; Benzalkonium Compounds - pharmacology; CD3 Complex - analysis; CD4-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - cytology; Cyclosporine - pharmacology; Detergents - pharmacology; Guinea Pigs; Ileum - chemistry; Ileum - cytology; Ileum - drug effects; Ileum - innervation; Immunosuppressive Agents - pharmacology; Male; Mice; Myenteric Plexus - chemistry; Myenteric Plexus - cytology; Myenteric Plexus - drug effects; Phosphopyruvate Hydratase - analysis; Proto-Oncogene Proteins c-fos - analysis; Proto-Oncogene Proteins c-jun - analysis; Proto-Oncogene Proteins c-myc - analysis; Rabbits; S100 Proteins - analysis; Thiolester Hydrolases - analysis; Ubiquitin Thiolesterase
• ISSN: 0302-766X; 1432-0878
• DOI: 10.1007/s004410050872

Ablation of rat myenteric plexus with benzalkonium chloride has provided a model of intestinal aganglionosis, but the degenerative responses are not well understood. We examined the effects of this detergent on neurons and glia, including expression of c-Myc, c-Jun, JunB, and c-Fos, and on immunocytes in the guinea-pig ileum. Benzalkonium chloride (0.1%) or saline was applied to the serosal surface of distal ileum. Tissues were analyzed 2, 3, or 7 days later and compared with cyclosporine-treated and untreated animals. More than 90% of myenteric neurons were destroyed in ileal segments 3-7 days after benzalkonium-chloride treatment. Glia withdrew processes from around neurons after 2 days and were mostly gone after 3 days. Neuronal c-Myc began to disappear while c-Fos, c-Jun, and JunB were evident in some neuronal nuclei after 2 or 3 days. After 3 days, widespread apoptosis was evident in the myenteric plexus. Populations of T cells, B cells, and macrophage-like cells in untreated and saline-treated myenteric plexuses were substantially increased 3 and 7 days after benzalkonium-chloride treatment. Cyclosporine delayed significant neuronal loss. We conclude that a variety of degenerative mechanisms may be active in this model, including an immune response which may actively contribute to tissue destruction.