RESUMEN
Neuronal abnormalities have been described in the intestine of helminth-infected rats. However, the physiological ramifications of these changes have not been determined. Here, we examined epithelial ion secretion, indicated by increases in short-circuit current (Isc), evoked by electrical transmural stimulation (TS) of enteric nerves in Ussing-chambered jejunal tissues from Nippostrongylus brasiliensis-infected rats. Rats were examined at 10 and 35 days post-infection (p.i.); non-infected rats served as controls. TS resulted in significantly reduced ion secretion in jejunum from 10 day p.i. rats compared to controls or jejunum from 35 day p.i. rats. The TS response in tissue from infected rats had, unlike controls, no cholinergic component. Tissues from both non-infected and infected rats were equally responsive to the muscarinic agonist bethanechol, suggesting that the cholinergic defect was neuronal and not an inability of the epithelium to respond to cholinergic stimulation. However, increases in Isc evoked by exogenous substance P (SP) in tissue from rats 10 day p.i. were reduced in magnitude to approximately 25% of control values. Concomitant with these physiological changes, tissue from infected rats contained increased amounts of substance P immunoreactivity and intestinal sections displayed increased numbers of substance P-immunoreactive nerve fibre profiles at both 10 and 35 days p.i. Thus, following N. brasiliensis infection there is a shift in the enteric nervous system away from cholinergic to non-cholinergic regulation, associated with increased amounts of the pro-inflammatory neuropeptide, substance P. We speculate that changes in neuronal structure and function are intimately involved in the co-ordinated multicellular response to intestinal parasitic infection and subsequent gut recovery.
Asunto(s)
Electrólitos/metabolismo , Sistema Nervioso Entérico/fisiopatología , Yeyuno/metabolismo , Nippostrongylus , Infecciones por Strongylida/fisiopatología , Animales , Atropina/farmacología , Betanecol/farmacología , Estimulación Eléctrica , Epitelio/fisiología , Mucosa Intestinal/química , Mucosa Intestinal/metabolismo , Yeyuno/química , Yeyuno/inervación , Masculino , Agonistas Muscarínicos/farmacología , Antagonistas Muscarínicos/farmacología , Inhibidores de Proteasas/farmacología , Ratas , Ratas Sprague-Dawley , Infecciones por Strongylida/parasitología , Sustancia P/análisis , Sustancia P/farmacología , Tetrodotoxina/farmacologíaRESUMEN
This study compared the tissue distribution and cellular expression of Ia antigen in jejunal and ileal epithelium at various stages of intestinal inflammation produced by infecting rats with the nematode parasite Nippostrongylus brasiliensis. Tissues were examined at Day 0 (control), Day 4 (early), Day 10 (acute), and Day 16 (recovering). Frozen sections were stained with the MRC OX-4 anti-Ia monoclonal antibody using an immunoperoxidase technique. Control jejunal sections demonstrated positive epithelial Ia expression mainly in the mid-regions of the villi. The stain appeared to be mostly intracellular in the supranuclear area; the basolateral membrane stained faintly. At Day 4, a greater percentage of the epithelial cells expressed Ia, including those at the tips of the villi. The Day 10 sections demonstrated no staining at all of villus enterocytes, but the crypt epithelium was Ia positive. At Day 16, the pattern of Ia expression was similar to that seen in the early infection. In the ileum, stain was present in enterocytes over most of the villus and crypt regions except in the villus-crypt junction and did not change significantly during infection. We conclude that the changes in the expression of Ia antigen by intestinal epithelium are local to the site of infection and probably occur as a consequence of the host's inflammatory response.
Asunto(s)
Íleon/inmunología , Yeyuno/inmunología , Infecciones por Nematodos/inmunología , Animales , Epitelio/inmunología , Epitelio/parasitología , Antígenos de Histocompatibilidad Clase II/análisis , Humanos , Íleon/parasitología , Enfermedades Inflamatorias del Intestino/inmunología , Yeyuno/parasitología , Masculino , Nippostrongylus , Ratas , Ratas EndogámicasRESUMEN
We have employed a cultured crypt-like intestinal epithelial rat cell line (IEC-18) to assess whether killing by nonspecific cytotoxic cells contributes to epithelial cell destruction in Nippostrongylus brasiliensis (N.b.) infection. Spleen cells from N.b.-infected Sprague-Dawley rats, 11-13 days postinfection when villus atrophy and crypt hyperplasia were evident, killed IEC-18 in a 4-hr 51Cr-release assay. In contrast, intraepithelial leukocytes (IEL) from N.b.-infected rats showed decreased killing of IEC-18 compared to controls in a 16-hr assay. Spleen NK activity was increased in N.b.-infected rats whereas IEL NK activity was decreased. We conclude that direct cytotoxicity of crypt-like intestinal epithelial cells by nonspecific cytotoxic cells appears to play no significant role in intestinal injury in N.b. infection.