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PubMed1991

Predominant Paneth cell differentiation in an intestinal type gastric cancer.

A distinct morphological variant of a diffuse type adenocarcinoma of the stomach with Paneth cell differentiation is reported. The tumor was a Borrmann's Type III carcinoma measuring 6.0 x 5.5 cm at the body along the greater curvature. It was composed of Paneth cell- and endocrine cell differentiated cancer cells in addition to tubular and poorly differentiated adenocarcinoma cells. The Paneth cell differentiation was characterized histologically by cytoplasmic distinct coarse eosinophilic granules stained red with periodic acid-Schiff and Masson trichrome reagents and reddish brown with phosphotungstic acid hematoxylin, and electron microscopically by lysozyme in cytoplasmic electron dense granules. In addition, electron microscopy revealed acid mucin globules and various intermediate forms between Paneth granules and the mucin globules which might be regarded as abortive forms of Paneth granules presumably resulting from defective incorporation of lysozyme-positive mucosubstances into acid mucin. Endocrine differentiated cancer cells consisted of serotonin-, peptide YY-, and glucagon/glicentin-positive cells. The various cell phenotypes found in the present tumor could be explained on the basis of intestinal differentiation of gastric cancer.

Adenocarcinoma↗
PubMed2006

Paneth cell antimicrobial peptides: topographical distribution and quantification in human gastrointestinal tissues.

Antimicrobial peptides and proteins are key effectors of innate immunity, expressed both by circulating phagocytic cells and by epithelial cells of mucosal tissues. In the human small intestine, Paneth cells are secretory epithelial cells that express the antimicrobials human alpha-defensin-5 (HD5), HD6, lysozyme and secretory phospholipase A(2) (sPLA(2)), and recent studies have implicated reduced HD5 and HD6 expression levels in the pathogenesis of ileal Crohn's disease. However, expression levels of these molecules have not been determined routinely by techniques that readily permit quantitative comparisons of their distribution between tissues and samples. Using quantitative real-time PCR with external standards and Northern blot analysis, we compared expression levels of mRNA encoding these four Paneth cell antimicrobial peptides, as well as circulating human neutrophil defensins in several different gastrointestinal tissues and the bone marrow. HD5 and HD6 were the most abundant antimicrobials expressed in the small intestine. The concentration of HD5 mRNA is approximately 5 x 10(5) copies per 10ng RNA in the jejunum and ileum; HD6 mRNA levels were about six times lower than those of HD5. With the exception of low levels in the pancreas (10(3) copies/10 ng RNA), the expression of HD5 and HD6 in tissues other than small intestine was at or below detectable limits. The expression of sPLA2 and lysozyme mRNA was observed in the small intestine (approximately, 3 x 10(3) and 9 x 10(3) copies/10 ng RNA, respectively), but also in several other tissues. Lysozyme expression was high in the duodenum (10(5) copies/10 ng RNA), and the protein localized to both Brunner's glands in the lamina propria and Paneth cells. By comparison, the hematopoietic alpha-defensins HNP1-3 mRNA were detected at 6 x 10(5) copies per 10 ng RNA in the bone marrow. These quantitative RT-PCR data from healthy tissues represents the first quantitative topographical assessment of antimicrobial expression in the gastrointestinal tract and provides a means to directly compare expression levels between healthy tissues and disease specimens for multiple antimicrobial peptides.

Anti-Infective Agents↗
PubMed1986

Quantitative electron microscopic observations on Paneth cells of germfree and ex-germfree Wistar rats.

Ultrastructural changes of Paneth cells of germfree (GF) rats which had been inoculated with bacteria-containing feces from conventionally-reared (SPF) rats were quantitatively examined. 12 and 24 h after inoculation, the Paneth cells showed a striking decrease in the number of secretory granules and the occurrence of large vacuoles. Phagosomes containing bacteria were not seen. After 4 days, the secretory granules reaccumulated and smooth-surfaced apical vesicles increased in number. It is discussed that the large vacuoles may be related to membrane-retrieval events following the massive extrusion of secretory granules whereas the apical vesicles appear to serve this function when exocytosis is not pronounced. In addition to the large secretory granules ca. 10% of Paneth cell profiles contained a few dense-cored vesicles measuring about 150 nm in diameter which resemble peptidergic neurosecretory granules.

Animals↗
PubMed1989

Paneth cell adenoma of the stomach.

A case of Paneth cell adenoma of the stomach in a 75-year-old woman is reported. At histological examination, a tubular adenoma with low-grade (moderate) dysplasia was found. The dysplastic cells had distinct coarse cytoplasmic granules that stained red with eosin and PAS but were negative with alcian blue pH 2.5. The adenoma may have developed from paneth cells present in areas of preexisting intestinal metaplasia.

Adenoma↗
PubMed1975

The Paneth cell: a source of intestinal lysozyme.

An antiserum prepared against lysozyme isolated from mucosal scrapings of mouse small intestine was used to stain sections of mouse small intestine with the indirect fluorescent antibody technique. Mucosal fluorescence was confined to the base of the crypts of Lieberkuhn, where Paneth cells are located. After the intravenous administration of 4 mg of pilocarpine fluorescence was no longer found in the Paneth cell but in the crypt lumen. Perfusion studies confirmed these findings. The basal lysozyme output of 0-1 to 0-4 mug/ml was raised to peak rates of 1-8 to 6-5 mug/ml after the intravenous administration of 1 mg of pilocarpine. Our results demonstrate that the lysozyme of the succus entericus is, at least in part, derived from the Paneth cell, and is probably present in the Paneth cell granules. Its secretion is stimulated by pilocarpine. Our model could be very useful for studying the function of the Paneth cell, which probably forms part of an intestinal defence system.

Animals↗
PubMed2004

Degranulation of paneth cells via toll-like receptor 9.

The release of antimicrobial peptides and growth factors by Paneth cells is thought to play an important role in protecting the small intestine, but the mechanisms involved have remained obscure. Immunohistochemistry and immunofluorescence showed that Paneth cells express Toll-like receptor 9 (TLR9) in the granules. Injection of mice with oligonucleotides containing CpG sequence (CpG-ODNs) led to a down-modulation of TLR9 and a striking decrease in the number of large secretory granules, consistent with degranulation. Moreover CpG-ODN treatment increased resistance to oral challenge with virulent Salmonella typhimurium. Moreover, our findings demonstrate a sentinel role for Paneth cells through TLR9.

Adjuvants, Immunologic↗
PubMed1998

Absence of lysozyme (muramidase) in the intestinal Paneth cells of newborn infants with necrotising enterocolitis.

AIM: To determine immunocytochemically whether preterm and newborn infants with necrotising enterocolitis (NEC) show differences in numbers of lysozyme positive Paneth cells compared with normal controls, and to relate the findings to the possibility that lysozyme deficiency may facilitate the bacterial infections thought to be associated with this condition. METHODS: Tissues from 10 infants with NEC and from 11 matched controls were sectioned and stained immunocytochemically for lysozyme. Differences in the numbers of Paneth cells and degree of lysozyme positivity in the tissues were assessed. RESULTS: Tissues from NEC patients showed no, or very few, lysozyme positive Paneth cells, whereas controls showed strong positive staining. CONCLUSIONS: A deficiency or developmental defect in Paneth cells, resulting in an absence of lysozyme, may render the intestine more susceptible to bacterial infection, allowing organisms to adhere and translocate across the mucosa. Such enhancement of infection may contribute to the pathogenesis of NEC.

Bacterial Infections↗
PubMed1986

Postnatal changes in the distribution and elemental composition of Paneth cells in normal and corticosteroid-treated rats.

Paneth cells containing zinc-rich granules were found in the small intestine of 6-day-old rats. These cells were more numerous in older animals and were consistently most common in the distal ileum. The zinc content of granules from 10-day-old rats was similar to that found in adults (ca 300 mg atoms/kg dry weight) but no calcium could be detected. An injection of cortisone acetate at 5 days resulted in a premature increase in the numbers of Paneth cells in 10-day-old rats. The cell granules contained normal, adult levels of zinc, a calcium concentration of ca 400 mg atoms/kg dry weight and also an increased concentration of phosphorus.

Aging↗
PubMed1999

IV. Paneth cell antimicrobial peptides and the biology of the mucosal barrier.

The hypothesis that epithelial cells release preformed antibiotic peptides as components of mucosal innate immunity has gained experimental support in recent years. In the mammalian small intestine, Paneth cells secrete granules that are rich in alpha-defensins and additional antimicrobial peptides into the lumen of the crypt. The alpha-defensins are homologues of peptides that function as mediators of nonoxidative microbial cell killing in phagocytic leukocytes, and they are potent microbicidal agents in in vitro assays. Because certain mouse alpha-defensins stimulate cultured epithelial cells to secrete chloride ion, those peptides appear to be capable of interacting directly with the apical membranes of neighboring cells and perhaps influencing crypt physiology. In instances of crypt disruption or induced Paneth cell deficiency, crypt intermediate cells appear to compensate by accumulating and secreting Paneth cell antimicrobial peptides. Challenges for the future will be to understand the mechanisms of this epithelial plasticity and to show that Paneth cells contribute directly to innate immunity in the crypt microenvironment.

Animals↗
PubMed1993

Nuclear bodies in Paneth cells of the rat.

Three types of nuclear bodies were identified in the Paneth cells of rat small intestine: simple nuclear bodies (type I), small complex nuclear bodies (type III) and large complex nuclear bodies (type IV). The entire simple nuclear bodies and the capsules of complex nuclear bodies were composed of 5 nm filaments. The core of small complex nuclear bodies resembled the interchromatin, while the core of large complex nuclear bodies resembled the granular and fibrillar components of the nucleolus. The Paneth cells of the rat small intestine were found to be especially rich in nuclear bodies: about 80% of nuclear profiles contained one or more sections through nuclear bodies. We suggest that a large number of nuclear bodies in Paneth cells is related to a high rate of protein synthesis in these cells.

Animals↗
PubMedDate not supplied

Intestinal adenomas of Min-mice lack enterochromaffin cells, and have increased lysozyme production in non-Paneth cells.

BACKGROUND: Adenomatous polyposis coli (APC) are important in maintaining normal epithelial mucosa. Intestinal tissues with mutations in Apc have disturbed cell proliferation, differentiation and migration. Paneth and enterochromaffin cells were studied in the intestine and intestinal adenomas from Min-mice with heterozygote and homozygote mutations in Apc, respectively. MATERIALS AND METHODS: The presence of Paneth and enterochromaffin cells in normal intestine and adenomas from Min-mice was studied in sections stained with lysozyme/PAS and connexin32. RESULTS: Min-mice intestinal adenomas had an increased number of lysozyme-producing Paneth/goblet and non-Paneth cells and a reduced number of enterochromaffin cells. The large intestine had a significantly higher number of enterochromaffin cells than the small intestine and more were seen in the large intestine of Min- compared with wt-mice. CONCLUSION: Altered cell differentiation in adenomas might be caused by different response to Wnt-signalling, while an increased number of enterochromaffin cells in the large intestine is rather an effect of a heterozygous Apc(Min) mutation.

Adenomatous Polyposis Coli↗
PubMed1964

AN ELECTRON MICROSCOPE STUDY OF MATURE AND DIFFERENTIATING PANETH CELLS IN THE RAT, ESPECIALLY OF THEIR ENDOPLASMIC RETICULUM AND LYSOSOMES.

In an electron microsope study, the morphology of mature Paneth cells from the small intestine of adult rats is compared with that of differentiating Paneth cells from young rats 2 to 4 weeks old. All mature cells exhibit a marked polarity similar to that of other exocrine gland cells and contain a well developed endoplasmic reticulum, an elaborate Golgi complex, and numerous large secretory granules; they also possess an abundance of lysosomes. The most conspicuous occurrence in the process of differentiation is the development of the endoplasmic reticulum. The most immature Paneth cells possess an endoplasmic reticulum of the vesicular type, which, during maturation, is replaced by the characteristic lamellated ergastoplasm of the mature cell. At a certain stage of differentiation the cavities of the developing cisternae show numerous communications with the perinuclear space, suggesting an outgrowth of the ergastoplasm from the nuclear envelope. Furthermore, the cavities and the perinuclear space at this particular stage contain a material which shows a remarkable intrinsic periodicity. An identical periodicity was exhibited by material contained in Golgi cisternae and secretory granules. Lysosomes are also present in the differentiating cells.

Aging↗
PubMed2006

Paneth cells: leukocyte-like mediators of innate immunity in the intestine.

Paneth cells are secretory intestinal epithelial cells located at the base of the crypts of Lieberkühn in the small intestine. They display prominent cytoplasmic granules, containing antibacterial proteins such as lysozyme, secretory phospholipase A2 type IIA, and alpha-defensins, which are released into the intestinal lumen in response to a range of stimuli. In this, they resemble circulating leukocytes, which also elaborate and secrete lysozyme and alpha-defensins as part of an antibacterial defense function, and the resemblance is sustained at other levels. The cells also strongly and specifically express the NOD2 gene product, one of an emerging family of critical, intracellular mediators of innate immune responses, which is also highly expressed in peripheral blood mononuclear cells, and they express RNA for tumor necrosis factor alpha, a major myelomonocytic cell-derived cytokine, which has a crucial role in the pathogenesis of diseases such as rheumatoid arthritis and Crohn's disease (CD). Thus, these cells, which are derived from the pluripotent intestinal epithelial stem-cell lineage, are sessile, resident host-defense cells, which may share with leukocytes the beneficial function of secreting antimicrobial peptides, as well as the potentially harmful capacity for promoting inflammation and tissue damage. Paneth cells are most abundant in the distal small intestine, which is the region most frequently affected by CD, and there is great interest in the potential role of these cells in this condition. This brief review summarizes current knowledge and speculates on how the study of these fascinating cells might be advanced.

Animals↗
PubMed1988

Effect of live and heat-killed bacteria on the secretory activity of Paneth cells in germ-free mice.

Germ-free mice were given live or heat-killed facultative anaerobes, and the ultrastructure of ileal Paneth cells was quantitatively examined with special reference to secretory granules showing a bipartite substructure (central core and peripheral halo). After administering live or heat-killed bacteria, there was a decrease in the area occupied by the cores of secretory granules in Paneth cells, and exocytosed core material was observed in the crypt lumen. There were no changes in the area occupied by the halo of secretory granules. None of the examined Paneth cells phagocytosed bacteria. It is concluded that certain bacteria may affect the secretion of antibacterial agents contained in the secretory granules of Paneth cells.

Animals↗
PubMed1990

Paneth cells and coeliac disease--quantitative, morphometric analysis.

In semithin toluidine blue stained sections, investigated under the light microscope, the size and the shape of the Paneth cells, their nuclei and their granules was studied. The group of 10 patients suffering from the coeliac disease was compared with the control group (5 persons without gastrointestinal trouble). The results revealed a statistically significant increase in the size and shape alterations of the Paneth cells and increase in the number and size of their granules in the group of patients with the coeliac disease. This morphological findings prove higher functional activity of the Paneth cells in the coeliac disease. We can conclude that changes in the number, size and shape of the Paneth cells can be regarded as a non-specific defense reaction to this disease.

Adolescent↗
PubMed2003

Expression of NOD2 in Paneth cells: a possible link to Crohn's ileitis.

BACKGROUND AND AIMS: Genetic variation in NOD2 has been associated with susceptibility to Crohn's disease (CD) and specifically with ileal involvement. The reason for the unique association of NOD2 mutations with ileal disease is unclear. To identify a possible link, we tested expression of NOD2 in intestinal tissue of CD patients and controls. PATIENTS AND METHODS: Fifty five specimens of ileum or colon from 21 CD patients, seven ulcerative colitis (UC) patients, and five controls with pathology other than CD or UC were stained for NOD2 using an immunoperoxidase method. RESULTS: Using a monoclonal antibody against NOD2 developed in our laboratory, we detected uniform expression of NOD2 in terminal ileum Paneth cells from controls and patients as well as in metaplastic Paneth cells in the colon. Mechanical purification showed enriched expression of NOD2 mRNA in ileal crypts. In Paneth cells, NOD2 was located in the cytosol in close proximity to the granules that contain antimicrobial peptides. We detected minimal NOD2 in the villous epithelium of the ileum or in the colonic epithelium from both CD patients and controls. CONCLUSIONS: These results suggest a role for NOD2 in the regulation of Paneth cell mediated responses against intestinal bacteria and a plausible mechanism to explain the selective association of NOD2 mutations with ileal disease. The impaired capacity of CD associated mutations to sense luminal bacteria may result in increased susceptibility to certain gut microbes.

Adolescent↗
PubMed2002

Paneth cell trypsin is the processing enzyme for human defensin-5.

The antimicrobial peptide human alpha-defensin 5 (HD5) is expressed in Paneth cells, secretory epithelial cells in the small intestine. Unlike other characterized defensins, HD5 is stored in secretory vesicles as a propeptide. The storage quantities of HD5 are approximately 90 450 microg per cm2 of mucosal surface area, which is sufficient to generate microbicidal concentrations in the intestinal lumen. HD5 peptides isolated from the intestinal lumen are proteolytically processed forms--HD5(56-94) and HD5(63-94)--that are cleaved at the Arg55-Ala56 and Arg62-Thr63 sites, respectively. We show here that a specific pattern of trypsin isozymes is expressed in Paneth cells, that trypsin colocalizes with HD5 and that this protease can efficiently cleave HD5 propeptide to forms identical to those isolated in vivo. By acting as a prodefensin convertase in human Paneth cells, trypsin is involved in the regulation of innate immunity in the small intestine.

Amino Acid Sequence↗
PubMed1995

Ducts of esophageal glands proper and paneth cells in Barrett's esophagus: frequency in biopsy specimens.

The frequency of ducts of esophageal glands proper and Paneth cells was studied in endoscopic biopsy specimens obtained from 49 patients diagnosed as having Barrett's esophagus. Esophageal gland ducts were found in 5 (10%) of the subjects. Paneth cells were observed in 15 (31%) of the 49 patients, being located mainly among mucous cells of intestinalized crypts although a few were also noted in the surface epithelium. Since the presence of esophageal gland ducts in the columnar epithelium-lined mucosa is a pathognomonic feature of Barrett's esophagus, 10% of the patients reviewed were considered to have an unequivocal diagnosis of Barrett's esophagus. Barrett's mucosa showed histological features similar to incomplete-type intestinal metaplasia of gastric mucosa, except for the presence of Paneth cells.

Adult↗