Five intestinal defensins, termed cryptdins 1-5, have been purified from mouse small bowel, sequenced, and localized to the epithelium by immunohistochemistry. Although identified as members of the defensin peptide family by peptide sequencing, enteric defensins are novel in that four cryptdins have amino termini which are three to six residues longer than those of leukocyte-derived defensins. A fifth cryptdin is the first defensin to diverge from the previously invariant spacing of cysteines in the peptide structure. The most abundant enteric defensin, cryptdin-1, had antimicrobial activity against an attenuated phoP mutant of Salmonella typhimurium but was not active against the virulent wild-type parent. Immunohistochemical localization demonstrated that cryptdin-1, and probably cryptdins 2 and 3, occur exclusively in Paneth cells, where the peptides appear to be associated with cytoplasmic granules. Biochemical and immunologic analysis of the luminal contents of the small intestine suggest that cryptdin peptides are secreted into the lumen, similar to Paneth cell secretion of lysozyme. The presence of several enteric defensins in the intestinal epithelium, evidence of their presence in the lumen, and the antibacterial activity of cryptdin-1 suggest that these peptides contribute to the antimicrobial barrier function of the small bowel mucosa.
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15 August 1992
Article|
August 15 1992
Enteric defensins: antibiotic peptide components of intestinal host defense.
M E Selsted,
M E Selsted
Department of Pathology, College of Medicine, University of California, Irvine 92717.
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S I Miller,
S I Miller
Department of Pathology, College of Medicine, University of California, Irvine 92717.
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A H Henschen,
A H Henschen
Department of Pathology, College of Medicine, University of California, Irvine 92717.
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A J Ouellette
A J Ouellette
Department of Pathology, College of Medicine, University of California, Irvine 92717.
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M E Selsted
Department of Pathology, College of Medicine, University of California, Irvine 92717.
S I Miller
Department of Pathology, College of Medicine, University of California, Irvine 92717.
A H Henschen
Department of Pathology, College of Medicine, University of California, Irvine 92717.
A J Ouellette
Department of Pathology, College of Medicine, University of California, Irvine 92717.
Online ISSN: 1540-8140
Print ISSN: 0021-9525
J Cell Biol (1992) 118 (4): 929–936.
Citation
M E Selsted, S I Miller, A H Henschen, A J Ouellette; Enteric defensins: antibiotic peptide components of intestinal host defense.. J Cell Biol 15 August 1992; 118 (4): 929–936. doi: https://doi.org/10.1083/jcb.118.4.929
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