Paneth cells

Fig. 11.4. Model for cholinergic signalling in the intestinal mucosa, providing a possible rationale for AChE secretion by parasitic nematodes. ACh released from enteric cholinergic motor neurons stimulates chloride secretion, mucus secretion and Paneth cell exocytosis through muscarinic receptors. Secretory responses may be modulated by mast cell mediators, either directly or via the induction of neural reflex programmes. The role of muscarinic receptor-positive cells in the lamina propria of rats infected with N. brasiliensis is undetermined, as are potential mechanisms of trans-epithelial transport of the enzymes. Adapted from Cooke (1984).

Ouellette, A.J. and Selsted, M.E. (1996) Paneth cell defensins endogenous peptide components of intestinal host defense. FASEB Journal 10, 1280-1289. 

Satoh, Y., Ishikawa, K., Oomori, Y., Takeda, S. and Ono, K. (1992) Bethanechol and a G-protein activator, NaF/AlC13, induce secretory response in Paneth cells of mouse intestine. Cell and Tissue Research 269, 213-220. 

Elms, M. E. (1976). The Paneth cell population of the small intestine of the rat-effects of fasting and zinc deficiency on total count and on dithizone-reactive count. /. Pathol. 118, 183-191. 

Erlandsen, S. L., and Chase, D. G. (1972). Paneth cell function Phagocytosis and intracellular digestion of intestinal microorganisms. /. Ultrastruct. Res. 41, 296-318. 

The gastrointestinal system of zebrafish presents clear differences from the human system. The zebrafish does not possess a stomach, the intestine is continuous with the pharynx through a short esophagus, and no sphincters are present [61]. However, zebrafish have most of the cell types observed in the small intestine -absorptive, endocrine, goblet, and interstitial cells of Cajal, although Paneth cells are absent. Gut contractions are under the control of the enteric nervous systems, which respond to different pharmaceuticals in similar way as the mammalian counterpart. For example, zebrafish embryos can be used as predictor of emetic response to pharmaceuticals, one of the most commonly reported clinical adverse effects to be considered in the development of new dmgs [61]. 

Satchell DP, Sheynis T, Shirafuji Y, Kolusheva S, Ouellette AJ, Jelinek R. Interactions of mouse Paneth cell alpha-defensins and alpha-defensin precursors with membranes. 

An important role in the nonspecific cellular response is played by Paneth cells which line the bottom of the intestinal glands. Their granules contain compounds that can damage bacteria. These include a lysozyme which damages peptidoglycan, the basic structure of Gram positive bacterial cellular membrane secreted phospholipase A2 involved in lipopolysaccharide metabolism and a-defensins, cryptydins, which decompose bacterial proteins. 

Brodin B, Nielsen CU, Steffansen B, Frokjaer S (2002) Transport of peptidomimetic drugs by the intestinal di/tripeptide transporter, PepTl. Pharmacol Toxicol 90 285-296 Bry L, Falk P, Huttner K, Ouellette A, Midtvedt T, Gordon JI (1994) Paneth cell differentiation in the developing intestine of normal and transgenic mice. Proc Natl Acad Sci 91 10335-10339... 

Cryptdin-4, the most potent a-defensin from mouse Paneth cells... 

Figure 17 Three-dimensional structures of vertebrate antimicrobial peptides, (a) pardaxin from fish mucous glands (PDB code 1XC0) (b) cryptdin-4 from mouse Paneth cells (PDB code 2GW9) (c) retrocyclin-2, a synthetic peptide based on a human genome sequence (PDB code 2ATG) (an overlay of the 20 lowest energy structures is given to highlight the structural disorder associated with this laddered arrangment of the three disulphide bonds) and (d) fowlicidin-1 from chickens (PDB code 2AMN).

Jones, D., Bevins, C. Paneth cells of the human small intestine express an antimicrobial peptide gene. J Biol Chem 267 (1992) 23216-23225. 

Guanylin] Animals ex endocrine Paneth cells in Activates C-type PM GC... 

Paneth cells contribute to the maintenance of the gastrointestinal barrier, by secreting a number of antimicrobial molecules (alpha-defensins or cryptidins), as well as lysozyme and phospholipase A2. Their location, adjacent to crypt stem cells, suggests they have a role in defending epithelial cell renewal. 

Cell division and the subsequent differentiation give rise to several different types of cells, including the enterocyte and goblet cells. Other types that account for only about 1,0% of the epithelial ceils of the gut include endocrine cells, which produce hormones, and Paneth cells, which produces lysozyme, an antibacterial enzyme. The reason for the rapid turnover of the epithelial surface of the gut is the necessity of maintaining its function in the harsh environment of pancreatic enzymes. 

Suzuki K, Fukui H, Kayahara T, et al. Hesl-deficient mice show precocious differentiation of Paneth cells in the small intestine. Biochem Biophys Res Commun. 2005 328(l) 348-352. 

A number of studies have shown the association of gastric adenocarcinogenesis with intestinal metaplasia. Metaplasia means transformation of a mature form of cells into another type of mature cells in response to certain stimuli. In this case, gastric mucosal cells are converted to intestinal mucosal cells, especially goblet cells and Paneth cells. Indeed, it is believed that approximately one-third of all gastric adenocarcinoma is associated with intestinal metaplasia. " " ... 

Stappenbeck, T.S., Hooper, L.V., and Gordon, J.I. 2002. Developmental regulation of intestinal angiogenesisby indigenous microbes via Paneth cells. Proc. Natl Acad. Sci. USA99,15451—15455. 

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