Incidence of Paneth cells in minute tubular adenomas and adenocarcinomas of the large bowel.

This study attempted to demonstrate the incidence of Paneth cells within large bowel tubular adenoma and adenocarcinoma according to location and macroscopic appearance using minute tumors (up to 5 mm in size). We have shown that Paneth cells were sometimes seen in the early stage of the development of large bowel epithelial neoplasia. According to the macroscopic appearance (elevated or depressed type), in large bowel epithelial neoplasia, there was a statistical difference between the depressed type (32.5%, 14 of 40 cases) and the elevated type (16.6%, 24 of 145 cases) (Chi square analysis, p < 0.05) in the incidence of Paneth cells. Paneth cells were seen more frequently in adenocarcinoma (45.8%, 11 of 24 cases) than in tubular adenoma (16.8%, 27 of 161 cases), with a significant statistical difference (Chi square analysis, p < 0.01). According to location, in both tubular adenoma and adenocarcinoma, Paneth cells were more frequently observed in the proximal colon (tubular adenoma: p < 0.01, adenocarcinoma: p < 0.05, Chi square analysis).     

Renewal of Paneth cells in the small intestine of the mouse

The origin and fate of Paneth cells were examined in duodenum, jejunum and ileum of adult female mice, using radioautography after administration of ³H-thymidine either in a single injection or in drinking water for four days or as a continuous infusion for up to ten days. The tissues were fixed by perfusion with 4% paraformaldehyde. One-micron thick, Eponembedded single or serial sections were stained with Regaud's hematoxylin, radioautographed, and counterstained with safranin O. Mitosis of Paneth cells is never observed, nor are these cells ever labeled one hour after ³H-thymidine. Hence, Paneth cells do not divide. However, a few days after single injection or prolonged administration of ³H-thymidine, labeled Paneth cells appear. The first labeled cells have tiny granules but, as the cells age, larger and larger granules are observed. Adjacent to Paneth cells are slender undifferentiated cells which show frequent mitoses and early labeling. The evidence points to some of these cells transforming into Paneth cells. Since occasionally Paneth cells degenerate, the newly-formed ones would provide replacement for those which die, thus insuring the steady state of the Paneth cell population. The renewal of this population is characterized by a turnover time of about three weeks.     

Paneth cells and antibacterial host defense in neonatal small intestine

Paneth cells are specialized epithelia in the small bowel that secrete antimicrobial proteins. Paneth cells are vital to the innate immunity of the small bowel in adult mammals, but their role during neonatal infection of the small bowel is not well established. Dithizone selectively damages Paneth cells, and when dithizone-treated newborn rats are infected enterally with Escherichia coli, the numbers of E. coli cells in their jejunal and ileal lavage fluid are significantly increased compared to controls. The data support that Paneth cells are necessary for neonatal antibacterial defense.     

The distribution of argyrophile and argentaffin cells in the small intestine of rabbits.

The distribution of argentaffin and argyrophile cells has been studied in the small intestine of six rabbits. The conclusions are as follows: 1. The density of argentaffin and argyrophile cells is variable over the length of the small intestine. 2. Both types of cells are most numerous in the duodenum. 3. The overall pattern of distribution reveals a sharp fall in the density of these cells in the proximal one third, or so, of the small intestine. Thereafter, the curve of distribution is almost flat for argentaffin cells while there is a very gradual fall in the density of argyrophile cells. 4. The curve of distribution of both argentaffin and argyrophile cells show the presence of a number of waves of rising and falling density. 5. There are considerable species variations in the distribution of argyrophile and argentaffin cells.     

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.     

Neoplastic Paneth cells in the experimental murine carcinoma of the small intestine

The purpose of this study is to elucidate the participation of Paneth cells in experimentally induced adenocarcinoma of the intestine. The rats were fed with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) dissolved in drinking water ad libitum at a concentration of 100 micrograms/ml for 28 weeks. They were sacrificed 12 weeks after the last MNNG administration. A number of tumor cells containing large eosinophilic granules in their supranuclear cytoplasm (Paneth cells) were observed in about 20% of the experimentally induced adenocarcinoma of the small intestine. The granules were stained positively with Lendrum, periodic acid-Schiff, Masson's trichrome, and Mallory's phosphotungstic acid hematoxylin. Ultrastructurally, the granules were round, osmiophilic, and relatively even in size. We compared the morphologic features of the Paneth cell-containing small intestinal adenocarcinomas (Group I) with those without Paneth cells (Group II). Group I was distinguished from Group II by its better differentiation, larger tumor size and lower incidence of calcification. Although Paneth cells are extremely rare in human gastrointestinal carcinomas, twenty percent of MNNG-induced intestinal carcinomas harbor Paneth cells. The neoplastic Paneth cells in experimental carcinomas may differentiate from uncommitted cells in the deeper portion of the crypt.     

Distribution of diazo-positive (argentaffin) cells in the small intestine of rats of various ages

In unit lengths of longitudinally cut histological sections of the rat small intestine, the number of diazo-positive argentaffin cells was determined along with the number of other epithelial cells. From these results, the frequency of argentaffin cells among the epithelial cells was calculated. The number, as well as the frequency, was maximal in the proximal duodenum and progressively decreased to a minimum in the mid-intestine. Thereafter, it increased progressively caudally to reach a second maximum in the terminal ileum. The frequency in the terminal ileum was almost as high as in the proximal duodenum. When calculated for the duodenum of various age groups, it decreased from eight to two argentaffin cells per 1000 epithelial cells from newborn to adult ages respectively. It was calculated furthermore that the total number of diazo-positive argentaffin cells in the rat small intestine should be around six million. Considering that the argentaffin cells are renewed about every four days (Ferreira and Leblond, ′71), about 1.5 million of them should be formed as well as exfoliated daily. The cells in the villi were stained more intensely than in the crypts, indicating that the argentaffin cells accumulate granules as they migrate from the crypts toward the villus tips, where indeed, intensely stained exfoliating argentaffin cells were occasionally observed. It is suggested that the exfoliation of argentaffin cells full of granules may be a mode of secretion for 5-hydroxytryptamine into the intestinal lumen.     

Distribution and significance of the smooth muscle component in polyps of the large intestine

Immunocytochemical staining for alpha smooth muscle actin specifically reveals the distribution of the muscularis mucosae and pericryptal intramucosal smooth muscle fibers in the normal mucosa and polyps of the large intestine. In the latter, the muscular component is hyperplastic, especially in pedunculated polyps, which display a thick "muscular zone" at the top of the stalk. The diagnostic (and prognostic) significance of the distribution pattern of the muscular component in polyps, and in "early invasion" cases, is discussed.