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At least 19 recordsLinked to original sources
PubMed1977

Morphological study of the Paneth cell. Paneth cells in intestinal metaplasia of the stomach and duodenum of man.

The Peneth cells in intestinal metaplasia of stomach and the duodenum in human subjects were studied ultrastructurally, and the fine structures of these cells were compared. Paneth cells showed the ultrastructure of serozymogenic cells and secreted their secretory granules by merocrine process. The rod or tubular dense bodies were observed in the apical region of some Paneth cells. The structures may have some relation to the secretion of the secretory granules. The secretory granules with less dense layer in the periphery, which had never been described in the Paneth cell of man, were also observed. Morphologically intermediate cells between Paneth cell and goblet cell were found. Some of the Paneth cells might be phagocytized by undifferentiated crypt cells. The Paneth cells in intestinal metaplasia were fundamentally the same as those in duodenum at least in morphology. Difference between them was that Paneth cells with many phagolysosomes in the lower cytoplasm were observed more frequently in the duodenum than in intestinal metaplasia of the stomach. The physiological functions of the Paneth cell have been discussed.

Duodenal Diseases↗
PubMed2006

Expression of polymeric immunoglobulin receptor mRNA and protein in human paneth cells: Paneth cells participate in acquired immunity.

OBJECTIVE: Paneth cells are important effectors of intestinal innate immunity. It has been generally accepted that Paneth cells do not participate in the synthesis of polymeric immunoglobulin receptor (pIgR) or the secretion of immunoglobulin A (IgA) in the small intestine. However, we have previously shown that pIgR is specifically localized in Paneth cells of the rat small intestine. We therefore investigated the possibility that pIgR is also localized in human Paneth cells. METHODS: Double-labeled fluorescent immunohistochemistry and double-labeled fluorescent in situ hybridization were used to determine RNA and protein expression in normal human small intestine. RESULTS: Both pIgR mRNA and protein were colocalized with lysozyme in normal human Paneth cells. Furthermore, IgA was colocalized with lysozyme in the secretory granules of human Paneth cells. CONCLUSIONS: This is the first study to demonstrate that pIgR and IgA are colocalized in the secretory granules of human Paneth cells. These findings suggest that, in addition to their well-recognized role in innate immunity, Paneth cells are involved in IgA-mediated acquired immunity in the gastrointestinal tract. Furthermore, these results add to accumulating evidence that Paneth cells participate in intestinal inflammation.

Humans↗
PubMed1994

Monoclonal antibodies to a zinc-binding protein of rat Paneth cells.

Paneth cells are morphologically well characterized but their function has been not elucidated. Previously, we identified and purified a 90 KD zinc-binding protein (ZBPP-1) in rat intestine that was localized to Paneth cell granules, consistent with their high zinc content. To further elucidate the structure and function of ZBPP-1, we immunized Balb/c mice with purified ZBPP-1 and identified four independent monoclonal antibodies (MAb) producing MAb ZIP-1 (IgM), ZIP-2 (IgG1), ZIP-3 (IgM), and ZIP-4 (IgM). Immunohistochemistry (IHC) and immunoelectron microscopy (IEM) with these MAb showed positive staining of Paneth cell cytoplasmic granules. MAb ZBPP-1 also stained a population of mononuclear cells in the lamina propria of digestive tract mucosa and a few cells in spleen, presumably a subset of macrophages. These MAb will provide a useful tool to study the function of Paneth cells in human health and disease, since they cross-reacted with human intestinal Paneth cells and mucosal mononuclear cells.

Animals↗
PubMed1983

Morphologic unity of Paneth cells.

Paneth cells occurring in intestinal and extraintestinal sites were studied using various light microscopic techniques, including standard hematoxylineosin (HE)-stained histologic sections; a number of histochemical reactions, including the phosphotungstic acid-hematoxylin (PTAH) method; and immunohistochemical labeling for the presence of lysozyme using the peroxidase-antiperoxidase (PAP) method. Cells, identified on HE as Paneth cells, uniformly stained with PTAH and PAP-lysozyme. Further, all of the cases demonstrating epithelial cell lysozyme showed eosinophilic cytoplasmic granules, typical of Paneth cells, on HE sections. Lysozyme was demonstrated in benign and malignant ovarian tumors, as well as in a variety of ectopic intestinal sites and benign and malignant intestinal tumors, supporting the concept that the elaboration of lysozyme is a nonspecific feature of intestinal-cell differentiation and is not a response to a specific stimulus.

Cystadenocarcinoma↗
PubMed1990

Fibrillary cytoplasmic inclusions in neoplastic Paneth cells.

Paneth cell differentiation was investigated in two colorectal carcinomas. Ultrastructural study showed a range of granules and, in one case, fibrillary cytoplasmic inclusions. Similar inclusions in normal Paneth cells have been associated with zinc deficiency. However, there was no clinical evidence of abnormal zinc metabolism in this patient, nor were inclusions seen in adjacent non-neoplastic Paneth cells. It is speculated that these fibrillary inclusions might reflect an intrinsic zinc-related metabolic defect in the tumour cells.

Adult↗
PubMed1976

The influence of 400 r x-irradiation on the number and the localization of mature and immature goblet cells and Paneth cells in intestinal crypt and villus.

The influence of 400 R X-irradiation on the localization and the number of mature and immature goblet cells and Paneth cells in rat duodenal epithelium has been studied. At short times after irradiation, when the total proliferative activity in the crypts of Lieberkuhn is reduced, the proportion of mature and immature goblet cells of the total number of crypt cells was increased; also an absolute increase in the number of goblet cells in the crypts was found. The immature goblet cells were localized in the lower half of the crypt as in control animals, whereas the number of the mature cells increased over the whole crypt length. When the proliferative activity of the crypt cells increases again from 12 to 48 hr after irradiation the number of both types of goblet cells decreases. Between 48 and 72 hr, when the whole crypt is involved in proliferation, a second increase of both types of goblet cells was found. However, the localization of the immature goblet cells is no longer restricted to the lower half of the crypt but they also appear at the higher cell positions. On the villus no immature goblet cells were found and the changes in the numbers of mature goblet cells do reflect the changes induced by irradiation in the goblet cell population in the crypt. The absolute number and localization of Paneth cells did not change under the experimental conditions. The findings are discussed in relation to cell proliferation and differentiation processes in intestinal crypts.

Animals↗
PubMed2002

The multifaceted Paneth cell.

Paneth cells (PCs) were described over a century ago as granulated cells located at the base of small intestinal crypts, the 'crypts of Lieberkühn.' Various histochemical staining procedures were developed that identified PCs based on their distinctive granule-staining pattern. Early on, PCs were proposed to perform a specialized function other than absorption of digested nutrients, the predominant task of the small intestinal epithelium. Since then, many constituents of the PC granules have been biochemically characterized. The presence of various granule-associated antimicrobial substances and their release upon microbial challenge suggest that PCs function as specialized defense cells in the small intestine. Altered resistance to microbial infection in animal models with disrupted or augmented PC function provides further support for the host defense role of PCs. Other PC components suggest that PCs may also participate in the regulation of lumenal ionic composition, crypt development, digestion, and intestinal inflammation.

Animals↗
PubMed1979

Ultrastructural characteristics, secretory and phagocytotic activity of Paneth cells.

Paneth cells in the depth of Lieberkühn's crypts were studied ultrastructurally in three human jejunal biopsy material. Fine structural elements were observed indicative of phagocytosis. It is also assumed that the cells had regulatory function of normal intestinal flora. The importance of ultrastructural examinations of Lieberkühn's crypts under pathological conditions is emphasized.

Cell Nucleus↗
PubMed2000

Selective sparing of goblet cells and paneth cells in the intestine of methotrexate-treated rats.

Proliferation, differentiation, and cell death were studied in small intestinal and colonic epithelia of rats after treatment with methotrexate. Days 1-2 after treatment were characterized by decreased proliferation, increased apoptosis, and decreased numbers and depths of small intestinal crypts in a proximal-to-distal decreasing gradient along the small intestine. The remaining crypt epithelium appeared flattened, except for Paneth cells, in which lysozyme protein and mRNA expression was increased. Regeneration through increased proliferation during days 3-4 coincided with villus atrophy, showing decreased numbers of villus enterocytes and decreased expression of the enterocyte-specific genes sucrase-isomaltase and carbamoyl phosphate synthase I. Remarkably, goblet cells were spared at villus tips and remained functional, displaying Muc2 and trefoil factor 3 expression. On days 8-10, all parameters had returned to normal in the whole small intestine. No methotrexate-induced changes were seen in epithelial morphology, proliferation, apoptosis, Muc2, and TFF3 immunostaining in the colon. The observed small intestinal sparing of Paneth cells and goblet cells following exposure to methotrexate is likely to contribute to epithelial defense during increased vulnerability of the intestinal epithelium.

Animals↗
PubMed2001

Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease.

BACKGROUND AND AIMS: Intestinal epithelial cell derived antimicrobial peptides of the defensin family may play a major role in host defence against microorganisms. Our aims were to (i) isolate, characterise, and investigate the processing of human defensin 5 (HD-5) in normal Paneth cells and (ii) investigate expression of HD-5 in active inflammatory bowel disease (IBD). METHODS: Antiserum raised against chemically synthesised putative mature HD-5 was used for immunohistochemistry and purification of HD-5 from extracts of normal terminal ileal crypts. RESULTS: In normal and Crohn's disease terminal ileum, HD-5 immunoreactivity was seen in Paneth cells and in some villous epithelial cells. Normal colonic mucosa did not express HD-5 but HD-5 immunoreactivity was seen in cells in the colonic crypt region of many IBD samples. N-terminal amino acid sequence analysis of HD-5 purified from normal terminal ileal Paneth cells consistently showed the predicted sequence of the precursor form of the peptide. Following stimulation of isolated intact normal terminal ileal crypts, a truncated form of HD-5, with the N-terminal sequence GEDNQLAIS, was detected in the supernatant. CONCLUSIONS: (i) HD-5 is present only in the precursor form in normal terminal ileal Paneth cells and is processed to the mature form during and/or after secretion, (ii) some villous epithelial cells express HD-5, and (iii) HD-5 is expressed by metaplastic Paneth cells in the colon in IBD.

Animals↗
PubMed1980

Crohn's disease: transmission electron microscopic studies. I. Barrier function. Possible changes related to alterations of cell coat, mucous coat, epithelial cells, and Paneth cells.

Surgically resected specimens and grossly normal resection margins from patients with Crohn's disease and normal controls were studied by a variety of ultrastructural techniques. This work describes changes in three anatomic barriers--mucus, cell coat, and epithelial cells--found in this disease. As seen by transmission electron microscopy, mucus was increased in diseased areas as well as in the margins of resection. The thickness of the cell coat was moderately increased in resection margins but not in diseased areas. Detachment and losses of cell coat were noted in some diseased areas. A marked increase in cytoplasmic dense vesicles suggests increased losses and increased production of cell coat in diseased areas. Goblet cells and epithelial cells showed no consistent signs of cell injury. Epithelial cells in diseased areas had markedly shortened microvilli and an increase in lysosomes. Paneth cells were increased in number and showed both focal granule extrusion and cytoplasmic lysosomal inclusions. The possible significance of these findings in terms of barrier function and uptake phenomena is discussed.

Crohn Disease↗
PubMed2005

Immunocytochemical localization of secretory component in Paneth cell secretory granules-rat Paneth cells participate in acquired immunity.

With the marker of Paneth cells-lysozyme, secretory component (SC) immunoreactivity was demonstrated exclusively in Paneth cells of rat small intestine. The other types of epithelial cells (columnar, goblet, endocrine) were negative. On electron microscopic level, many SC-positive colloidal gold particles were found in rough endoplasmic reticulum, Golgi complexes, basal membrane and secretory granules of Paneth cells. These results suggest that SC is not a component of ingested immune complex, but a membrane receptor on Paneth cell. It may function as receptor for polymeric IgA and mediate its transport across the mucosal epithelium. Thus, Paneth cells are responsible for SC synthesis and participate in IgA-mediated acquired immunity in rat small intestine.

Animals↗
PubMed2002

Involvement of tumor necrosis factor alpha in intestinal epithelial cell proliferation following Paneth cell destruction.

BACKGROUND: An intravenous injection of diphenylthiocarbazone (dithizone), a zinc chelator, induces selective killing of Paneth cells which have a large amount of zinc in their cytoplasmic granules. A transient wave of intestinal epithelial cell proliferation occurs at 12 h after the injection. Paneth cells have tumor necrosis factor (TNF)-alpha protein in their cytoplasmic granules, and TNF-alpha has a proliferative effect on intestinal epithelial cells in vitro. The aim of this study is to clarify the in vivo role of TNF-alpha in intestinal epithelial cell proliferation using a dithizone-treated rat model. METHODS: Male Wistar rats received a dithizone (100 mg/kg of body weight) injection with or without TNF-alpha inhibitor, pentoxifylline (100 mg/kg), neutralizing anti-TNF-alpha antibody (2 mg/kg), or nuclear transcription factor kappaB (NF-kappaB) inhibitors: pyrrolidine dithiocarbamate (100 mg/kg) or N-acetyl-L-cystein (100 mg/kg). The activation of NF-kappaB was examined by the electrophoretic mobility shift assay, and cellular proliferation by BrdU labeling. RESULTS: Without any inhibitors, dithizone treatment evoked NF-kappaB activation in the ileal mucosa with its peak level at 2 h after the injection. TNF-alpha inhibition reduced the NF-kappaB activation, and blocked a transient wave of epithelial cell proliferation 12 h after the injection. NF-kappaB inhibitors also reduced the NF-kappaB activation and epithelial cell proliferation. CONCLUSIONS: TNF-alpha released from degenerated Paneth cells was, in part, responsible for the intestinal cell proliferation through the activation of NF-kappaB, suggesting its proliferative effect on intestinal epithelial cells.

Animals↗
PubMed2006

Enteropathy with loss of enteroendocrine and paneth cells in a patient with immune dysregulation: a case of adult autoimmune enteropathy.

Autoimmune enteropathy (AIE) is a relatively rare condition found most frequently in children. It presents with persistent watery diarrhea and malabsorption and may require total parenteral nutrition for nutritional support. Rare cases have been reported in adults. On histology, the small intestinal villi are flattened but lack the intraepithelial lymphocytosis of celiac disease. In children and rarely in adults, some cases are linked to the IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked inheritance). We report a 21-year-old man who presented with chronic persistent diarrhea for 4 years. The duodenal biopsies showed villous blunting, chronic inflammation, and decreased to absent goblet cells, Paneth cells, and endocrine cells by histology and electron microscopy. These changes are consistent with an AIE with involvement of non-enterocyte populations. Pathologists must be aware of the possibility of AIE in adults and consider it in the differential diagnosis of duodenitis, intraepithelial lymphocytosis, and small bowel villous flattening.

Adult↗
PubMed2000

Gallbladder Adenocarcinoma with Florid Neuroendocrine Cell Nests and Extensive Paneth Cell Metaplasia.

We report a unique case of gallbladder adenocarcinoma associated with florid neuroendocrine cell nests and extensive Paneth cell metaplasia that has not been described previously. The patient was a 79-yr-old woman with a pedunculated, polypoid mass in the gallbladder. Microscopically, the mass was composed at tumor cells showing tubular and papillary growth patterns, consistent with well-differentiated adenocarcinoma. One-third or more of the tumor cell showed Paneth cell appearance. Goblet cell-type tumors were also intermingled. In addition, neuroendocrine cell nests, that were connected to the neoplastic glands, were scattered throughout the stroma. lmmunohistochemically, the labeling index of MIB-1 in adenocarcinoma cells including Paneth cell-type carcinoma cells was approx 40%. Neuron-specific enolase, chromogranin A, and synaptophysin were positive in the neuroendocrine cells forming solid nests and intermingled within neoplastic glands. They were immunopositive for serotonin but negative for insulin, glucagon, somatostatin, and pancreatic polypeptide (PP). Although MIB-1-positive neuroendocrine cell nests were very few with weak staining, we think that the neuroendocrine cell nests were neoplastic in nature. The formation of the multifocal neuroendocrine nests may be a consequence of the trophic effects of unknown substance(s), which can promote serotonin producing neuroendocrine cells to proliferate. We postulate that Paneth cell-type carcinoma cells may be intimately related to such substance(s) in our case.

Journal Article↗
PubMed2005

Hes1-deficient mice show precocious differentiation of Paneth cells in the small intestine.

We have previously shown that Hes1 is expressed both in putative epithelial stem cells just above Paneth cells and in the crypt base columnar cells between Paneth cells, while Hes1 is completely absent in Paneth cells. This study was undertaken to clarify the role of Hes1 in Paneth cell differentiation, using Hes1-knockout (KO) newborn (P0) mice. Electron microscopy revealed premature appearance of distinct cells containing cytoplasmic granules in the intervillous region in Hes1-KO P0 mice, whereas those cells were absent in wild-type (WT) P0 mice. In Hes1-KO P0 mice, the gene expressions of cryptdins, exclusively present in Paneth cells, were all enhanced compared with WT P0 mice. Immunohistochemistry demonstrated increased number of both lysozyme-positive and cryptdin-4-positive cells in the small intestinal epithelium of Hes1-KO P0 mice as compared to WT P0 mice. Thus, Hes1 appears to have an inhibitory role in Paneth cell differentiation in the small intestine.

Animals↗