PANETH CELL DEFENSINS - ENDOGENOUS PEPTIDE COMPONENTS OF INTESTINAL HOST-DEFENSE

Paneth cells are epithelial granulocytes at the base of the crypts of Lieberkuhn in the small intestine of many mammalian species, These sec retory cells contribute to mucosal barrier function by the apical rele ase of granules containing a variety of antimicrobial products, includ ing peptides termed cryptdins, for crypt defensins. In mice, six Panet h cell defensins have been characterized at the peptide level that hav e potent antimicrobial activities equivalent to or greater than that o f rabbit neutrophil defensin NP-1. Cryptdin peptides that differ only by single amino acid substitutions have been shown to exhibit a high d egree of specificity against certain target microorganisms, Cryptdins are coded by separate, two-exon genes that are located on chromosome 8 in both mice and humans. Human Paneth cells contain high levels of tw o different defensin mRNAs, but in mice at least 19 cryptdin isoforms are predicted from cDNA sequencing data, The mouse cryptdin-4 gene is expressed with positional specificity along the longitudinal intestina l axis, and cryptdin genes are active in the intestinal epithelium pri or to Paneth cell differentiation. Accordingly, Paneth cell defensins are early markers of crypt ontogeny and are therefore useful in studie s of lineage determination in the intestinal epithelium, Because crypt dins mediate innate immunity in the hostile environment of the intesti nal lumen, it should be of interest to define biochemical and biophysi cal attributes that adapt these peptides to barrier function of mucosa l surfaces.