ENTERIC DEFENSINS

Paneth cells in the crypts of Lieberkuhn of the small intestine releas e granules that contain antimicrobial proteins and peptides into the c rypt lumen, alpha-Defensins, or cryptdins, are abundant in mouse and h uman Paneth cell granules, and evidence suggests that they contribute to gastrointestinal host defense and influence the crypt microenvironm ent. The alpha-defensins are basic, 3 to 4 kD amphipathic peptides tha t contain three invariantly paired cysteines that determine some of th e biochemical properties of the peptide family. The mouse and human in testinal peptides are potent antimicrobial agents with selective activ ities against several microbial species. Studies of mouse cryptdin iso forms show that amino acid substitutions at positions on the peptide s urface can modulate antimicrobial activity, suggesting that these posi tions may be involved in peptide-target cell interactions. The known a lpha-defensins are coded by individual two-exon genes that are cluster ed on chromosome 8 in mice and humans. In mice, Paneth's cell alpha-de fensin genes are expressed differentially during neonatal development and along the longitudinal axis of the small intestine. Human Paneth c ell a-defensin HD-5 also is expressed in female genitourinary tract ep ithelium, and mouse cryptdins are found in Sertoli cells and Leydig ce lls of the testis. Thus, Paneth cell a-defensins are likely effecters of innate immunity in the small intestine and also on other mucosal su rfaces.