Paneth cells and necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a common and devastating disease of premature infants. Immaturity of the innate immune system of the gut is central to the pathogenesis of NEC. Recent studies suggest a key role for Paneth cells in this disease. Addressing basic questions on the development and function of immature Paneth cells may shed light on the puzzling pathophysiology of NEC. Current animal models of NEC are limited in their capacity to answer these questions.     

The Paneth cell in disease

A systematic study of the distribution of Paneth cells in disease of the small and large intestine is described. In disease of the small intestine and appendix there is usually a fall in the number of Paneth cells normally present. Occasionally, as in Crohn's disease, there may be proliferation. In disease of the colon the number of Paneth cells is unaltered in functional and developmental disorders and increased in the inflammatory and neoplastic diseases. It is suggested that the Paneth cell proliferation originates from stem cells in the colon.

The significance of an increase in Paneth cells is discussed and it is suggested that in ulcerative colitis it may produce a self-perpetuating and destructive state.

     

Paneth cells in Barrett's esophagus

Paneth cells were identified in esophageal biopsies from 4 patients with Barrett's epithelium of the specialized columnar type. These cells were identical to human intestinal Paneth cells by light microscopy, electron microscopy, and histochemical staining reactions. Retrospective review of biopsies from 8 additional cases with esophageal specialized columnar epithelium yielded 2 further cases with Paneth cells. The presence of Paneth cells, along with goblet cells, suggests that specialized columnar type epithelium in the esophagus may be a form of highly differentiated intestinalization.     

Paneth cells and necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a common and devastating disease of premature infants. Immaturity of the innate immune system of the gut is central to the pathogenesis of NEC. Recent studies suggest a key role for Paneth cells in this disease. Addressing basic questions on the development and function of immature Paneth cells may shed light on the puzzling pathophysiology of NEC. Current animal models of NEC are limited in their capacity to answer these questions.     

Trypsin-like immunoreactivity in human Paneth cells

Human intestinal Paneth cells characterized by their content of lysozyme were shown to contain cationic trypsin immunoreactivity. This trypsin-like immunoreactivity was shown in the Paneth cells at their normal localization at the basis of the crypts of Lieberkühn and also in Paneth cells of metaplastic areas in gastric mucosa. This original finding is a further indication of a resemblance between Paneth and acinar pancreatic cells.     

Paneth细胞与炎症性肠病

Paneth细胞是一种分布于肠腺底部的肠黏膜分化上皮细胞,可向腺体分泌生长因子和抗微生物肽如溶菌酶和防御素。随着对炎症性肠病（IBD）发病机制研究的不断深入,已发现Paneth细胞及其分泌的抗微生物分子参与了肠道黏膜屏障的破坏,可致自身免疫失衡,启动肠道炎症反应,从而引起肠道黏膜功能的改变,在IBD的触发和复发中起一定作用。Paneth细胞在IBD中是参与免疫防御还是促进免疫损伤,目前仍在研究讨论中。     

Paneth cells in intestinal physiology and pathophysiology

Small intestinal mucosa is characterised by villus forming connective tissues with highly specialised surface lining epithelial cells essentially contributing to the establishment of the intestinal border.In order to perform these diverse functions,spatially distinct compartments of epithelial differentiation are found along the crypt-villus axis,including Paneth cells as a highly specialised cell type.Paneth cells locate in crypts and assist undifferentiated columnar cells,called crypt base columnar cells,and rapidly amplifying cells in the regeneration of absorptive and secretory cell types.There is some evidence that Paneth cells are involved in the configuration and function of the stem cell zone as well as intestinal morphogenesis and crypt fission.However,the flow of Paneth cells to crypt bottoms requires strong Wnt signalling guided by EphB3 and partially antagonised by Notch.In addition,mature Paneth cells are essential for the production and secretion of antimicrobial peptides including α-defensins/cryptdins.These antimicrobials are physiologically involved in shaping the composition of the microbiome.The autophagy related 16-like 1(ATG16L1) is a genetic risk factor and is involved in the exocytosis pathway of Paneth cells as well as a linker molecule to PPAR signalling and lipid metabolism.There is evidence that injuries of Paneth cells are involved in the etiopathogenesis of different intestinal diseases.The review provides an overview of the key points of Paneth cell activities in intestinal physiology and pathophysiology.     

克罗恩病与潘氏细胞的研究进展

克罗恩病(CD)是病因尚不明确的炎症性肠病(IBD)。其主要发生在回肠末端及邻近结肠,潘氏细胞(PC)是小肠的特征性细胞,此文通过阐述已经发现的PC相关的研究进展,如防御素、NOD2、TCF-4、ATG16L1等,探讨这一方面可能致CD的机制,为CD的病因研究提供帮助。     

Comparative histochemical study of insulinocytes and Paneth cells

Histochemical reactions of insulocytes and Paneth cells of rabbits and rats were investigated following the injection of the agents selectively affecting the above cells, as well as of glucose, a specific stimulant of insulin secretion. The data obtained suggest a functional relation between the pancreatic islet cells and the intestinal cryptic basal regions, which is mediated by the mechanisms, involved in regulation of the glycemic level.     

Reduced Paneth cell alpha-defensins in ileal Crohn's disease

The pathogenesis of Crohn's disease (CD), an idiopathic inflammatory bowel disease, is attributed, in part, to intestinal bacteria that may initiate and perpetuate mucosal inflammation in genetically susceptible individuals. Paneth cells (PC) are the major source of antimicrobial peptides in the small intestine, including human alpha-defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC alpha-defensins compromises mucosal host defenses and predisposes patients to CD of the ileum. We report that patients with CD of the ileum have reduced antibacterial activity in their intestinal mucosal extracts. These specimens also showed decreased expression of PC alpha-defensins, whereas the expression of eight other PC products either remained unchanged or increased when compared with controls. The specific decrease of alpha-defensins was independent of the degree of inflammation in the specimens and was not observed in either CD of the colon, ulcerative colitis, or pouchitis. The functional consequence of alpha-defensin expression levels was examined by using a transgenic mouse model, where we found changes in HD5 expression levels, comparable to those observed in CD, had a pronounced impact on the luminal microbiota. Thus, the specific deficiency of PC defensins that characterizes ileal CD may compromise innate immune defenses of the ileal mucosa and initiate and/or perpetuate this disease.     

Defensins and Paneth cells in inflammatory bowel disease

Defensins are antimicrobial peptides produced by professional phagocytes, Paneth cells, and intestinal epithelial cells. In addition to their potent antimicrobial activity, defensins can also modulate the function and movement of neutrophils, monocytes, T-lymphocytes, dendritic cells, and epithelial cells. Paneth cells are equipped with multiple defensins and antimicrobial proteins and usually reside in the small intestine. This review highlights the diverse functions of defensins and changes in defensin expression and Paneth cell proliferation in Crohn's disease, ulcerative colitis, and animal models of inflammatory bowel disease. Current data favor the hypothesis that defensins and Paneth cells may play important roles in the maintenance of intestinal immune homeostasis through 2 distinct mechanisms. The first mechanism is to act as effector molecules and cells against pathogenic microbes, while the second is to regulate host immune cell functions.     

Paneth Cell Alertness to Pathogens Maintained by Vitamin D Receptors

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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.