PANETH CELLS AND DEFENSINS

Paneth cells (reviewed by Cunliffe and colleagues^1,2) are granulated epithelial cells found at the base of small intestinal crypts. They are most numerous in the terminal ileum and are not found in the normal colon. They secrete a variety of antimicrobial peptides and proteins, including α-defensins, lysozyme, and secretory phospholipase A₂ (sPLA₂), in response to bacterial products and cholinergic agents. There is a link between intestinal inflammation and Paneth cell number. In mouse models of enteric infection, Paneth cell hyperplasia occurs in response to signals from activated T cells, in mouse models of ileocolitis there is Paneth cell metaplasia, and in inflammatory bowel disease, Paneth cell metaplasia is also seen in the colon. Parasite infestations also induce an increase in the number of Paneth cells in the murine small intestine.

Defensins (reviewed by Ganz³) are a family of small (29–45 amino acid) cationic antimicrobial peptides that are divided into two main classes, the α- and β-defensins, on the basis of their disulphide bond pairing pattern. They are encoded by single genes as prepropeptides, which are then processed to mature active forms. The mammalian defensin genes probably evolved from a single ancestral gene but because of selection pressure and rapid evolution, comparisons between species is difficult.⁴

Six α-defensins have been identified in humans: four are neutrophil peptides and two human defensins (HD-5 and HD-6) are expressed in intestinal Paneth cells. HD-5 is expressed in Paneth cells of the duodenum, jejunum, and ileum, but is not found in the normal stomach or colon. In cases of gastritis, Crohn’s colitis, and ulcerative colitis, HD-5 is expressed in metaplastic Paneth cells.

In vitro, α-defensins have broad spectrum …