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

Abstract

(Gut 2001;48:176-185)

Fibroblast Growth Factor Receptor-3 (FGFR-3) Regulates Expression of Paneth Cell Lineage-specific Genes in Intestinal Epithelial Cells through both TCF4/β-Catenin-dependent and -independent Signaling Pathways

“…ProHD5 is cleaved either as it exits the cell or in the lumen after it is secreted. Trypsin, also present as an inactive zymogen in Paneth cells, is believed to be the serine protease that converts proHD5 to the mature active form in the intestine (2,45). Although Caco2 cells produce trypsin, they also express ␣1-antitrypsin (47,48).…”

“…Our current work demonstrates that signaling through FGFR-3, which is abundantly expressed by Caco2 cells (43) Paneth cells, located at the base of intestinal crypts in close proximity to stem cells, are key effectors of innate immunity, safeguarding the intestinal stem cell compartment from microbial invasion through their production of microbicidal peptides and enzymes (3,44). HD5, a major defensin of human Paneth cells, is synthesized as a prepropeptide that must be proteolytically cleaved to generate the fully active mature peptide (2,45,46). Paneth cells store proHD5 in their granules.…”

“…They are most abundant in the terminal ileum and not present in the normal colon (1,2). Paneth cells are key effectors of innate mucosal immunity (3)(4)(5).…”

Defensins in Ulcerative Colitis

“…Enteric -defensins occur exclusively in Paneth cells in normal small bowel (Cunliffe et al, 2001;Ouellette et al, 1999;Ouellette et al, 2000;Porter et al, 1997b;Selsted et al, 1992 ). Myeloid and Paneth cell -defensins genes differ in that genes expressed in cells of myeloid origin consist of three exons, whereas those expressed in Paneth cells have only two exons (Bevins et al, 1996;Huttner et al, 1994;Jones & Bevins, 1992;Jones & Bevins, 1993;Lala et al, 2003).…”

Human Defensins in HIV Infection: Friends or Foes?

“…Elevation of HNPs has been reported in the vaginal mucosa of women with N. gonorrhoeae (GC), T. vaginalis, or C. trachomatis (CT) (Simhan et al, 2007;Valore et al, 2006;Wiesenfeld et al, 2002), suggesting their role in mucosal immunity against infection in vivo (Heine et al, 1998;Wiesenfeld et al, 2002). HD5, the most abundant AMPs in the small intestine, is constitutively expressed by paneth cells but can be found in other tissues such as the salivary glands, the female genital tract and the inflamed large bowel (Cunliffe et al, 2001;Fahlgren et al, 2003;Fellermann and Stange, 2001;George et al, 2008;Quayle et al, 1998;Salzman et al, 2007;Svinarich et al, 1997). Rhesus macaque, an animal model used for studying HIV pathogenesis, expresses six paneth cell defensins but their coding sequences are distinct from HD5 and HD6 (Tanabe et al, 2004).…”