Soup Kettle Topics: Gut and digestive physiology

Title: The Enteric Nervous System: A Second Brain
Author: Gershon, M. D.; (Date: Jul 15, 1999)
Journal: Hosp Pract (Off Ed); V. 34; Issue: 7; Pages: 31-2, 35-8, 41-2 passim

Abstract: Once dismissed as a simple collection of relay ganglia, the enteric nervous system is now recognized as a complex, integrative brain in its own right. Although we still are unable to relate complex behaviors such as gut motility and secretion to the activity of individual neurons, work in that area is proceeding briskly–and will lead to rapid advances in the management of functional bowel disease.
Notes: Journal Article
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Author Address: Department of Anatomy and Cell Biology, Columbia University College of Physicians and Surgeons, New York, USA.

Title: A Critical Role for Eotaxin in Experimental Oral Antigen-Induced Eosinophilic Gastrointestinal Allergy
Author: Hogan, S. P.; Mishra, A.; Brandt, E. B.; Foster, P. S.; Rothenberg, M. E.; (Date: Jun 6, 2000)
Journal: Proc Natl Acad Sci U S A; V. 97; Issue: 12; Pages: 6681-6

Abstract: Despite marked advances in the understanding of allergic responses, the mechanisms regulating gastrointestinal allergy are not very well understood. We have developed a model of antigen-induced eosinophil-associated gastrointestinal allergy and characterized the role of eotaxin and IL-5. Challenge of allergen-sensitized mice with oral allergen, in the form of enteric-coated beads, resulted in marked allergen-specific IgG(1) and IgE, Th(2)-type (IL-4 and IL-5) cytokine production, and eosinophil accumulation in the blood and small intestine. In the genetic absence of eotaxin, a chemokine constitutively expressed in the gastrointestinal tract, eosinophil recruitment into the small intestine was ablated, and these mice developed enhanced eosinophil accumulation in the blood compared with wild-type mice. Interestingly, in the absence of IL-5, allergen challenge promoted partial eosinophil accumulation into the small intestine and a decline in circulating eosinophil levels. Collectively, these results establish that the accumulation of gastrointestinal eosinophils is antigen induced, can occur independent of IL-5, and provides a molecular mechanism to explain the dichotomy between peripheral blood and tissue eosinophilia. Furthermore, eotaxin is identified as a critical regulator of antigen-induced eosinophilic inflammation in the gastrointestinal tract.
Notes: Journal Article
Author Address: Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

Title: Peyer’s Patch Eosinophils: Identification, Characterization, and Regulation by Mucosal Allergen Exposure, Interleukin-5, and Eotaxin
Author: Mishra, A.; Hogan, S. P.; Brandt, E. B.; Rothenberg, M. E.; (Date: Aug 15, 2000)
Journal: Blood; V. 96; Issue: 4; Pages: 1538-44

Abstract: The gastrointestinal immune system is traditionally thought to be composed of lymphocytes located within Peyer’s patches and the lamina propria. We have recently reported that eosinophils also reside in the gastrointestinal tract during healthy states, in particular, within the lamina propria, and that these cells substantially increase after oral allergen exposure. We now demonstrate the presence of eosinophils in Peyer’s patches and characterize the signals that regulate the accumulation of eosinophils in Peyer’s patches. In contrast to the lamina propria, intestinal Peyer’s patches have very low levels of eosinophils under healthy states. However, elevated levels of interleukin-5 (IL-5), generated by transgenic or pharmacologic approaches, result in a dramatic increase in eosinophil levels in Peyer’s patches. Most eosinophils are located in the outer cortex and interfollicular regions of the Peyer’s patches. To dissect the mechanism of eosinophil trafficking to Peyer’s patches, the role of eotaxin was examined. Mice transgenic for IL-5 and genetically deficient in eotaxin were found to have reduced levels of eosinophils in Peyer’s patches compared with IL-5-transgenic mice. To prove that eosinophils also traffic to Peyer’s patches in wild-type mice, allergic hypersensitivity was induced and Peyer’s patches were examined. Exposure to mucosal allergen promoted marked accumulation of eosinophils in Peyer’s patches and this process was attenuated in eotaxin-deficient mice. In summary, these data demonstrate that elevated levels of IL-5 and mucosal allergen exposure promote eotaxin-dependent eosinophil trafficking to Peyer’s patches. These studies suggest that eosinophils may cooperate with lymphocytes in the development of mucosal immune responses in the gastrointestinal tract. (Blood. 2000;96:1538-1544)
Notes: Journal Article
Author Address: Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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