Human norovirus targets enteroendocrine epithelial cells in the small intestine.

Human noroviruses are a major cause of diarrheal illness, but pathogenesis is poorly understood. Here, we investigate the cellular tropism of norovirus in specimens from four immunocompromised patients. Abundant norovirus antigen and RNA are detected throughout the small intestinal tract in jejunal and ileal tissue from one pediatric intestinal transplant recipient with severe gastroenteritis. Negative-sense viral RNA, a marker of active viral replication, is found predominantly in intestinal epithelial cells, with chromogranin A-positive enteroendocrine cells (EECs) identified as a permissive cell type in this patient. These findings are consistent with the detection of norovirus-positive EECs in the other three immunocompromised patients. Investigation of the signaling pathways induced in EECs that mediate communication between the gut and brain may clarify mechanisms of pathogenesis and lead to the development of in vitro model systems in which to evaluate norovirus vaccines and treatment.

Role of regenerating islet-derived proteins in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an inflammatory disorder of the gastrointestinal tract that affects millions of patients worldwide. It has a complex and multifactorial etiology leading to excessive exposure of intestinal epithelium to microbial antigens, inappropriate activation of the immune system and ultimately to the damage of intestinal tissues. Although numerous efforts have been made to improve the disease management, IBD remains persistently recurring and beyond cure. This is due largely to the gaps in our understanding of the pathogenesis of IBD that hamper the development of timely diagnoses and effective treatment. However, some recent discoveries, including the beneficial effects of interleukin-22 (IL-22) on the inflamed intestine, have shed light on a self-protective mechanism in IBD. Regenerating islet-derived (REG/Reg) proteins are small secretory proteins which function as IL-22's downstream effectors. Mounting studies have demonstrated that IBD patients have significantly increased REG expressions in the injured intestine, but with undefined mechanisms and roles. The reported functions of REG/Reg proteins in intestinal homeostasis, such as those of antibacterial, anti-inflammatory and tissue repair, lead us to discuss their potential mechanisms and clinical relevance in IBD in order to advance IBD research and management.

Enteroendocrine cells-sensory sentinels of the intestinal environment and orchestrators of mucosal immunity.

The intestinal epithelium must balance efficient absorption of nutrients with partitioning commensals and pathogens from the bodies' largest immune system. If this crucial barrier fails, inappropriate immune responses can result in inflammatory bowel disease or chronic infection. Enteroendocrine cells represent 1% of this epithelium and have classically been studied for their detection of nutrients and release of peptide hormones to mediate digestion. Intriguingly, enteroendocrine cells are the key sensors of microbial metabolites, can release cytokines in response to pathogen associated molecules and peptide hormone receptors are expressed on numerous intestinal immune cells; thus enteroendocrine cells are uniquely equipped to be crucial and novel orchestrators of intestinal inflammation. In this review, we introduce enteroendocrine chemosensory roles, summarize studies correlating enteroendocrine perturbations with intestinal inflammation and describe the mechanistic interactions by which enteroendocrine and mucosal immune cells interact during disease; highlighting this immunoendocrine axis as a key aspect of innate immunity.

The zinc finger protein CG12744 is essential for differentiation and regeneration after infection in the adult Drosophila midgut.

Pluripotent stem cell activity is essential to maintain regeneration and homeostasis in the Drosophila midgut following environmental challenges. Although multiple pathways have been implicated in epithelial renewal, the underlying regulatory mechanisms and correlations between relevant genes and pathways remain elusive. In this study, we show that the zinc finger protein CG12744 plays an important role in the differentiation and regeneration of epithelial cells in response to oral infection with Erwinia carotovora carotovora 15. Knocking down CG12744 in enteroblasts decreased the post-infection proportion of enteroblasts and enterocytes and increased the post-infection number of enteroendocrine cells. In addition, in precursors, CG12744 affected the Osa, jun-N-terminal kinase and bone morphogenetic protein signaling pathways to control enterocyte differentiation. Finally, CG12744 maintained epithelial architecture and cell fate in enterocytes following an acute infectious challenge.

Changes in small intestinal chromogranin A-immunoreactive cell densities in patients with irritable bowel syndrome after receiving dietary guidance.

Chromogranin A (CgA) is a common marker for enteroendocrine cells in the gut, and CgA-immunoreactive cell densities are abnormal in patients with irritable bowel syndrome (IBS). The majority of patients with IBS report that their symptoms develop after consuming certain foodstuffs. In the present study, we investigated the effects of dietary guidance on the total enteroendocrine cell densities in the small intestine, as detected by CgA. A total of 14 patients with IBS underwent a gastroscopy with duodenal biopsies and 11 of them also underwent a colonoscopy, with biopsy samples obtained from the ileum. Fourteen control subjects were also included. Each patient received 3 sessions of dietary guidance. Gastroscopies and colonoscopies were performed on both the controls and patients with IBS (at baseline and at 3-9 months after receiving guidance). Biopsy samples obtained from the duodenum and ileum were immunostained for CgA using the avidin-biotin complex (ABC) method and were quantified using computerized image analysis. The density of CgA-immunoreactive cells in the duodenum (mean ± SEM values) in the control subjects was 235.9 ± 31.9 cells/mm2; in the patients with IBS, the density was 36.9 ± 9.8 and 103.7 ± 16.9 cells/mm2 before and after they received dietary guidance, respectively (P=0.007). The density of CgA-immunoreactive cells in the ileum in the control subjects was 47.4 ± 8.3 cells/mm2; in the patients with IBS, the density was 48.4 ± 8.1 and 17.9 ± 4.4 cells/mm2, before and after they received dietary guidance, respectively (P=0.0006). These data indicate that changes in CgA-immunoreactive cell densities in patients with IBS after receiving dietary guidance may reflect a change in the densities of the small intestinal enteroendocrine cells, which may contribute to an improvement in the IBS symptoms.

Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the small bowel in patients with severe irritable bowel syndrome.

BACKGROUND: Inflammation and immune activation have repeatedly been suggested as pathogentic factors in irritable bowel syndrome (IBS). The driving force for immune activation in IBS remains unknown. The aim of our study was to find out if the obligate intracellular pathogen Chlamydia could be involved in the pathogenesis of IBS. METHODS: We studied 65 patients (61 females) with IBS and 42 (29 females) healthy controls in which IBS had been excluded. Full thickness biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum were stained with a monoclonal antibody to Chlamydia lipopolysaccharide (LPS) and species-specific monoclonal antibodies to C. trachomatis and C. pneumoniae. We used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify enteroendocrine cells, macrophages, dendritic, and mast cells, respectively. RESULTS: Chlamydia LPS was present in 89% of patients with IBS, but in only 14% of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also positive for C. trachomatis major outer membrane protein (MOMP). Staining for C. pneumoniae was negative in both patients and controls. Chlamydia LPS was detected in enteroendocrine cells of the mucosa in 90% of positive biopsies and in subepithelial macrophages in 69% of biopsies. Biopsies taken at different time points in 19 patients revealed persistence of Chlamydia LPS up to 11 years. The odds ratio for the association of Chlamydia LPS with presence of IBS (43.1; 95% CI: 13.2-140.7) is much higher than any previously described pathogenetic marker in IBS. CONCLUSIONS: We found C. trachomatis antigens in enteroendocrine cells and macrophages in the small bowel mucosa of patients with IBS. Further studies are required to clarify if the presence of such antigens has a role in the pathogenesis of IBS.

Immunocytochemical study of gastrintestinal endocrine cells in insectivorous bats (Mammalia: Chiroptera) / Estudo imunocitoquímico das células endócrinas gastrintestinais de morcegos insetívoros (Mammalia: Chiroptera)

The regional distribution and relative frequency of endocrine cells in the stomach and intestine of Phyllostomidae: Lonchorhina aurita and Molossidae: Molossus molossus bats were studied immunohistochemically. Three types of immunoreactive (IR) endocrine cells - to serotonin (5-HT), gastrin (GAS) and enteroglucagon (GLUC) - were found in the gastric mucosa and four types of IR cells were identified in the intestinal mucosa. This study showed an interespecfic difference in the regional distribution and relative frequency of endocrine cells in the Chiropteran alimentary tract.

A distribuição regional e a freqüência relativa das células endócrinas no estômago e intestino dos morcegos insetívoros Phyllostomidae: Lonchorhina aurita e Mormoopidae: Molossus molossus foram estudadas pelo método de imunohistoquímica. Três tipos de células endócrinas imunorreativas (IR) à serotonina (5-HT), gastrina (GAS) e enteroglucagon (GLUC) foram localizadas na mucosa gástrica e quatro tipos de células endócrinas IR à 5-HT, GAS, colecistoquinina (CCK) e GLUC foram identificadas na mucosa intestinal. Este estudo mostrou uma diferença interespecífica na distribuição regional e na freqüência relativa das células endócrinas no trato alimentar de Chiropteros.

Induction of pro-inflammatory programs in enteroendocrine cells by the Toll-like receptor agonists flagellin and bacterial LPS.

Enteroendocrine cells are hormone-secreting cells spread along the intestinal epithelium. Their principal function is to promote the digestion of food. However, little is known about other functions that these cells may play, since they are difficult to study as a whole endocrine organ due to their diffuse localization. It is known that the intestinal epithelial barrier is actively involved in the host defense against pathogen invasion. Here we applied gene expression profiling to characterize the response of the human LCC-18 enteroendocrine cell line to physiological and pathological stimuli mimicked by fatty acids (FAs), flagellin and LPS exposure. We observed that these cells participate in an innate immune reaction to pathogens through the expression of pro-inflammatory factors (i.e. CXCL1 and 3 and IL-32) that we could validate by molecular and proteomic approach. Interestingly, IL-32 has been recently found over-expressed in the inflamed mucosa of patients affected by inflammatory bowel disease. This is very important because modifications of enteroendocrine cells during intestinal inflammation have been so far considered as secondary effects of the inflammatory status rather than due to direct pathogen/enteroendocrine cell interaction. As expected, FAs exposure up-regulates pro-differentiative genes and the production of cholecystokinin but it does not enhance the expression of pro-inflammatory genes. The present observations enlighten a new aspect of the cross talk between immune and endocrine system and suggest enteroendocrine cells as important contributors of inflammatory processes occurring in the gut in response to pathogen exposure and direct enhancers of the inflammatory status associated with human inflammatory bowel disease.

A comparative immunohistochemical study of endocrine cells in the digestive tract of two frugivorous bats: Artibeus cinerius and Sturnira lilium.

The purpose of the present study was to examine the serotonin (5-hydroxytryptamine, 5-HT), gastrin (GAS), cholecystokinin (CCK) and glucagon (GLUC) endocrine cells in the gastrointestinal tract of frugivorous Phillostomidae bats, Sturnira lilium and Artibeus cinerius, to clarify the correlation between distribution of cell types and their relative frequency, with feeding habits. Five portions of the gastrointestinal tract--fundus, pilorus, and three parts of the intestine, I, II and III--were examined. Most of the immunoreactive cells in the stomach and intestine were of triangular, oval or piriform shape. Serotonin-immunoreactive cells were most commonly found in the S. lilium intestine I (66.6+/-9.9) and the A. cinerius intestine III (35+/-18). Gastrin-immunoreactive cells were the most abundant cell type in the pyloric glands of both species. They were more numerous in A. cinerius (126.9+/-27.4) than in S. lilium (75.8+/-1.8). CCK-immunoreactive cells were found in the alimentary tract epithelia at moderate frequencies in both species. GLUC-immunoreactive cells were detected at very low or low frequencies. This study suggests that there is a correlation between endocrine cell distribution and frequency, and the feeding habits of the bats.

Enteroendocrine cells express functional Toll-like receptors.

Intestinal epithelial cells (IECs) provide a physical and immunological barrier against enteric microbial flora. Toll-like receptors (TLRs), through interactions with conserved microbial patterns, activate inflammatory gene expression in cells of the innate immune system. Previous studies of the expression and function of TLRs in IECs have reported varying results. Therefore, TLR expression was characterized in human and murine intestinal sections, and TLR function was tested in an IEC line. TLR1, TLR2, and TLR4 are coexpressed on a subpopulation of human and murine IECs that reside predominantly in the intestinal crypt and belong to the enteroendocrine lineage. An enteroendocrine cell (EEC) line demonstrated a similar expression pattern of TLRs as primary cells. The murine EEC line STC-1 was activated with specific TLR ligands: LPS or synthetic bacterial lipoprotein. In STC-1 cells stimulated with bacterial ligands, NF-kappaB and MAPK activation was demonstrated. Furthermore, the expression of TNF and macrophage inhibitory protein-2 were induced. Additionally, bacterial ligands induced the expression of the anti-inflammatory gene transforming growth factor-beta. LPS triggered a calcium flux in STC-1 cells, resulting in a rapid increase in CCK secretion. Finally, conditioned media from STC-1 cells inhibited the production of nitric oxide and IL-12 p40 by activated macrophages. In conclusion, human and murine IECs that express TLRs belong to the enteroendocrine lineage. Using a murine EEC model, a broad range of functional effects of TLR activation was demonstrated. This study suggests a potential role for EECs in innate immune responses.

Immunohistochemical study on the neuroendocrine system of the digestive tract of turbot, Scophthalmus maximus (L.), infected by Enteromyxum scophthalmi (Myxozoa).

In recent years a new parasite, causing severe losses, has been detected in farmed turbot, Scophthalmus maximus (L.), in Northwestern Spain. Dead fish showed emaciation and cachexia caused by severe necrotizing enteritis, which affected all areas of the digestive tract. The parasite was classified as a myxosporean and named Enteromyxum scophthalmi. This study was designed to assess the response of the turbot neuroendocrine system against E. scophthalmi infection. Immunohistochemical tests were applied to sections of the gastrointestinal tract of uninfected and E. scophthalmi-infected turbot, and the presence of cholecystokinin (CCK-8), serotonin (5-HT), substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) were documented. A higher abundance of both endocrine epithelial cells (ECs) and nerve cell bodies and fibres for CCK-8, 5-HT and SP were recorded in the gastrointestinal tract of infected turbot, whereas VIP-like substance decreased. The results indicate that E. scophthalmi infection in turbot induced changes in the neuroendocrine system, which may cause alterations in gut motility, electrolyte and fluid secretion, and vascular and immune functions.

Pernicious anemia and widespread absence of gastrointestinal endocrine cells in a patient with autoimmune polyglandular syndrome type I and malabsorption.

CONTEXT: Autoimmune polyglandular syndrome type I (APS I) is characterized by multiple endocrine gland failures, with other manifestations such as gastrointestinal (GI) symptoms. OBJECTIVE: The objective of the study was to study the histopathological and immunological findings in the GI mucosa of a patient with typical features of APS I, malabsorption, and pernicious anemia. DESIGN AND PATIENT: Biopsies from the GI tract of a patient with APS I were immunostained with chromogranin for GI endocrine cells (GIECs). Blinded slides were graded for numbers of endocrine cells. Normal gastric mucosa was exposed to the patient's serum to test for circulating anti-GIEC and antiparietal cell antibodies using indirect immunofluorescence. SETTING: The study was conducted at the Departments of Pediatrics and Medical Gastroenterology in an academic medical center. RESULTS: The patient's GI mucosa demonstrated absence of GIECs throughout, including gastric gastrin-secreting cells, and her laboratory tests for serum gastrin levels were low normal. Both GIECs and parietal cells were absent in her gastric corpus. The patient's serum contained anti-GIEC antibody but no antiparietal cell antibody. CONCLUSIONS: These observations suggest that GIECs in APS I are subject to an autoimmune destruction that can cause widespread GIEC loss. This could explain the GI dysfunctions that are often noted in the syndrome including malabsorption and atrophic gastric changes with pernicious anemia. We also hypothesize that absence of gastric parietal cells may result mainly from hypogastrinemia that is mainly the loss of gastrin-secreting cells rather than from immune-mediated destruction of parietal cells like that seen in the atrophic gastritis associated with adult-onset pernicious anemia.

The regional distribution and relative frequency of gastrointestinal endocrine cells in the nude mice, Balb/c-nu/nu: an immunohistochemical study.

The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal (GI) tract - fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum of the nude mouse, Balb/c-nu/nu were studied with immunohistochemical method using six types of anti-sera against serotonin, gastrin, cholecystokinin (CCK)-8, somatostatin, glucagon and human pancreatic polypeptide (hPP). All of six types of immunoreactive (IR) cells were identified. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of GI tract. Serotonin-IR cells were detected throughout the whole GI tract and they showed the highest frequency in the pylorus. Gastrin-IR cells were restricted to the pylorus and duodenum with numerous and a few frequencies, respectively. CCK-8-IR cells were also restricted to the pylorus, duodenum and jejunum with numerous, a few and rare frequencies, respectively. Somatostatin-IR cells were demonstrated throughout the whole GI tract except for the colon and rectum, and they showed the highest frequency in the fundus. In addition, glucagon- and hPP-IR cells were restricted to the fundus and rectum, respectively with a few frequencies. In conclusion, the general distribution patterns and relative frequency of GI endocrine cells of the nude mouse, Balb/c-nu/nu was similar to that of other strains of mice. However, some strain and/or species-dependent unique distributions and frequencies of endocrine cells were also observed especially for somatostatin- and hPP-IR cells.

An immunohistochemical study of the gastrointestinal endocrine cells in the ddY mice.

The distributions and frequencies of some endocrine cells in the gastrointestinal (GI) tract of ddY mice were studied with immunohistochemical method using 7 types of antisera against bovine chromogranin (BCG), serotonin, gastrin, cholecystokinin (CCK)-8, somatostatin, glucagon and human pancreatic polypeptide (HPP). All of 7 types of immunoreactive (IR) cells were identified. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open typed cell) while cells showing round in shape (close typed cell) were found in the intestinal gland and stomach regions occasionally. Their relative frequencies were varied according to each portion of GI tract. BCG-IR cells were demonstrated throughout whole GI tract except for the cecum and they were most predominant in the fundus and pylorus. Serotonin-IR cells were detected throughout whole GI tract and they were most predominant cell types in this species of mice. Gastrin-IR cells were restricted to the pylorus and CCK-8-IR cells were demonstrated in the pylorus, duodenum and jejunum with numerous frequencies in the pylorus. Somatostatin-IR cells were detected throughout whole GI tract except for the cecum and rectum and they showed more numerous frequencies in the stomach regions. In addition, glucagon-IR cells were restricted to the fundus, duodenum and jejunum with rare frequencies, and HPP-IR cells were restricted to the rectum only with rare frequency. In conclusion, some strain-dependent unique distributional patterns of gastrointestinal endocrine cells were found in GI tract of ddY mice.

Endocrine cells in gastric carcinoma and adjacent mucosa. An immunohistochemical and ultrastructural study.

Endocrine cells are often found in human gastric carcinoma and may be recognized by the immunoreactivity of their chromogranin A, peptides and biogenic amines content. Anti-chromogranin A was used to investigate the morphology of endocrine cells using light and electron microscope immunohistochemical techniques. The hormone content of endocrine cells was examined in both tumour tissue and tumour-adjacent mucosa. It was found that the endocrine cells in tumour tissue were malignant, often had amphocrine differentiation and did not resemble a normal cell type. The hormone content of endocrine cells in tumour tissue seldom corresponded to the hormonal content of endocrine cells in tumour-adjacent mucosa. In intestinal-type carcinoma and in some parts of diffuse-type gastric carcinomas, endocrine cell hyperplasia and an alteration of the differentiation in the tumour-adjacent mucosa were discovered. The distribution of endocrine cells in the tumour tissue was different in both types of gastric carcinoma. The results reported here suggest that endocrine cell differentiation of malignant endocrine cells in human gastric carcinoma develops in a different way from that of endocrine cells in tumour-adjacent mucosa, and as a result, diverse hormonal products may appear in tumour tissue.

TrkA and TrkC neurotrophin receptor-like proteins in the lizard gut.

The tyrosine kinase proteins (Trk), encoded by the trk family of proto-oncogenes, mediate, in mammals, the action of neurotrophins, a family of growth factors acting on the development and maintenance of the nervous system. Neurotrophins and their specific receptors, TrkA, TrkB and TrkC, seem to be phylogenetically well preserved but, in reptiles, data regarding the occurrence of Trk-like proteins are very scarce, especially in non-nervous organs. Western blot analysis demonstrated that the lizard gut contains TrkA- and TrkC-like, but not TrkB-like, proteins. Consistently, TrkA- and TrkC-like immunoreactivity were both observed in neurons of the anterior intestine, whereas endocrine cells of the stomach and anterior intestine only displayed TrkA-like immunoreactivity. These results demonstrate for the first time the occurrence of Trk-like proteins in non-neuronal tissues of reptilians and provide further evidence for the evolutionary preservation of the molecular mass and cell distribution of Trk neurotrophin receptor-like proteins in the gut of vertebrates.

Increased intracellular content of enteroglucagon in proximal colon is related to intestinal adaptation to germ-free status.

Changes in the frequency of endocrine cells are evidence of intestinal adaptation to germ-free (GF) status. Not only the distribution of these cells along the intestine, but also the differences in intracellular content of these regulatory peptides may be explored to explain functional and structural aspects of GF intestinal adaptation. Focusing on the endocrine L-cells, we analyzed the intracellular content of enteroglucagon (EG) and peptide YY (PYY) throughout the intestine of the 14 GF and 14 conventional (CV) mice by using immunohistochemistry and the supra-optimal dilution technique. The percentage of EG-immunoreactive cells, but not of PYY-immunoreactive cells stained at supra-optimal dilution was significantly higher in the proximal colon of GF mice than in the CV counterparts (P < 0.05). Since the content of co-stored PYY did not differ between GF and CV mice, the higher content of EG was compatible with a selective cellular response. Moreover, in the cecum of GF mice, the density of EG-immunoreactive cells was significantly higher than that of PYY-immunoreactive cells (P < 0.05). These results are consistent with preferential production of EG by L-cells at the expense of PYY in the proximal colon and in the enlarged cecum of GF mice. In addition, they may reflect the dynamics of the GF intestinal epithelium and/or be correlated with the higher serum levels of these peptides. The role of endocrine cells needs to be better studied in human and other experimental adaptative conditions in order to elucidate the regulatory mechanisms of intestinal functions.

Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome.

BACKGROUND AND AIMS: Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS. METHODS: Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls. RESULTS: In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p<0.001) compared with controls. Gut permeability, as assessed by the lactulose/mannitol ratio, was significantly elevated, initially and at 12 weeks (p<0.005). CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. At visit 1, EC numbers were positively correlated with CD3 counts (r=0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p<0.001), as was gut permeability (p<0.01). CONCLUSION: Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.

Células enteroendocrinas intraepiteliales en ciego y apéndice de conejos sensibilizados con ovoalbumina / Intraepithelial enteroendocrine cells in cecum and appendix from ovalbumin sensitized rabbits

Las células enteroendócrinas se relacionan con la motilidad, secreción y absorción de nutrientes. Actualmente está en estudio su relación con la respuesta inmune. El ciego y el apéndice del conejo, contienen en su luz bacterias y nutrientes en distintas etapas de digestión, con potencial acción antígenica. En el presente trabajo se evalúan las modificaciones en número y distribución de las células enteroendócrinas intraepiteliales en ciego y apéndice cecal de conejos sensibilizados con ovoalbúmina (OVA). Se utilizaron conejos neozelandeses adultos divididos en dos grupos, G1: grupo control (n=10). G2: sensibilizados vía intraperitoneal con OVA (n=10). Muestra de ciego y apéndice se fijaron en formol buffer al 10 por ciento marcándose las células enteroendócrinas con anticuerpo monoclonal anti-cromogranina A. En cada animal se contaron 400 campos microscópicos a mayor aumento, refiriéndose el número de células enteroendócrinas cada 100 enterocitos. En ciego se consideró epitelio superficial y criptal, mientras que en apéndice, epitelio superficial, criptas superficiales y criptas profundas. En epitelio superficial de ciego se hallaron 1,6 CEI/100 enterocitos en epitelio superficial y 3/100 en criptas. En G2 6 CEI/100 en epitelio superficial y 12/100 en criptas. La diferencia entre G1 y G2 fue estadísticamente significativa (p<0,05). En apéndice el epitelio superficial del G1 mostró 5,2/100 mientras que en G2 fue de 5.4/100 (no significativo). Las criptas superficiales evidenciaron 8,5/100 (G1) y 11.3/100 (G2) (p<0,05). En criptas profundas 4,9/100 (G1) y 8,5/100 (G2) (p<0,05). En los animales sensibilizados se detectó aumento significativo en la cantidad de células enteroendócrinas en ambos órganos. Dicho incremento podría atribuirse a un aumento de los gránulos intracitoplasmáticos o a la diferenciación de células generatrices a células APUD, como respuesta a la sensibilización.