Previous Article | Next Article 
Infect Immun. 1992 September; 60(9): 3556-3565
Cryptdins: antimicrobial defensins of the murine small intestine.
P B Eisenhauer,
S S Harwig and
R I Lehrer
Department of Medicine, UCLA School of Medicine 90024.
ABSTRACT
Paneth cells are specialized small intestine epithelial cells that contain lysozyme, possess phagocytic properties, and secrete cytoplasmic granules into the intestinal crypt lumen after the entry of bacteria. Recent studies by Ouellette and associates (A. J. Ouellette, R. M. Greco, M. James, D. Frederick, J. Naftilan, and J. T. Fallon, J. Cell Biol. 108:1687-1695, 1989) indicated that murine Paneth cells produce prodefensin mRNA, but the properties of its peptide product were not reported. We purified two closely related defensins, cryptdin 1 and cryptdin 2, from a subcellular fraction of murine small intestine cells that was enriched in Paneth cells. Both peptides contained 35 amino acid residues, including the characteristic defensin "signature" of six invariantly conserved cysteines. Cryptdins 1 and 2 were approximately 90 to 95% homologous to each other and to the carboxy-terminal domain of the 93-amino-acid defensin precursor, cryptdin A, described by Ouellette and associates (Ouellette et al., J. Cell Biol. 108:1687-1695, 1989). Both cryptdins exerted bactericidal activity against Listeria monocytogenes EGD and Escherichia coli ML-35p in vitro. Their potency exceeded that of human neutrophil defensin HNP-1 but was considerably lower than that of NP-1, a defensin produced by rabbit neutrophils and alveolar macrophages. Both cryptdins killed mouse-avirulent Salmonella typhimurium 7953S (phoP) much more effectively than its phoP+, mouse-virulent, isogenic counterpart, S. typhimurium 14028S. Our data indicate that mouse intestinal prodefensins are processed into 35-amino-acid mature defensins (cryptdins) with broad-spectrum antimicrobial properties. The production of defensins and lysozyme by Paneth cells may enable them to protect the small intestine from bacterial overgrowth by autochthonous flora and from invasion by potential pathogens that cause infection via the peroral route, such as L. monocytogenes and Salmonella species.
Infect Immun. 1992 September; 60(9): 3556-3565
This article has been cited by other articles:
-
Hamilton, A., Popham, D. L., Carl, D. J., Lauth, X., Nizet, V., Jones, A. L.
(2006). Penicillin-binding protein 1a promotes resistance of group B streptococcus to antimicrobial peptides.. Infect. Immun.
74: 6179-6187
[Abstract]
[Full Text]
-
Kobayashi, K. S., Chamaillard, M., Ogura, Y., Henegariu, O., Inohara, N., Nunez, G., Flavell, R. A.
(2005). Nod2-Dependent Regulation of Innate and Adaptive Immunity in the Intestinal Tract. Science
307: 731-734
[Abstract]
[Full Text]
-
Cunliffe, R. N., Mahida, Y. R.
(2004). Expression and regulation of antimicrobial peptides in the gastrointestinal tract. J. Leukoc. Biol.
75: 49-58
[Abstract]
[Full Text]
-
Zhang, H., Porro, G., Orzech, N., Mullen, B., Liu, M., Slutsky, A. S.
(2001). Neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose-related fashion. Am. J. Physiol. Lung Cell. Mol. Physiol.
280: L947-L954
[Abstract]
[Full Text]
-
Cunliffe, R N, Rose, F R A J, Keyte, J, Abberley, L, Chan, W C, Mahida, Y R
(2001). 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. Gut
48: 176-185
[Abstract]
[Full Text]
-
Ogawa, H., Fukushima, K., Sasaki, I., Matsuno, S.
(2000). Identification of genes involved in mucosal defense and inflammation associated with normal enteric bacteria. Am. J. Physiol. Gastrointest. Liver Physiol.
279: G492-G499
[Abstract]
[Full Text]
-
CUNLIFFE, R N, MAHIDA, Y R
(2000). Antimicrobial peptides in innate intestinal host defence. Gut
47: 16-17
[Full Text]
-
Tani, K., Murphy, W. J., Chertov, O., Salcedo, R., Koh, C. Y., Utsunomiya, I., Funakoshi, S., Asai, O., Herrmann, S. H., Wang, J. M., Kwak, L. W., Oppenheim, J. J.
(2000). Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens. Int Immunol
12: 691-700
[Abstract]
[Full Text]
-
Ouellette, A. J., Darmoul, D., Tran, D., Huttner, K. M., Yuan, J., Selsted, M. E.
(1999). Peptide Localization and Gene Structure of Cryptdin 4, a Differentially Expressed Mouse Paneth Cell alpha -Defensin. Infect. Immun.
67: 6643-6651
[Abstract]
[Full Text]
-
BEVINS, C L, MARTIN-PORTER, E, GANZ, T
(1999). Defensins and innate host defence of the gastrointestinal tract. Gut
45: 911-915
[Full Text]
-
Castle, M., Nazarian, A., Yi, S. S., Tempst, P.
(1999). Lethal Effects of Apidaecin on Escherichia coli Involve Sequential Molecular Interactions with Diverse Targets. J. Biol. Chem.
274: 32555-32564
[Abstract]
[Full Text]
-
Drouault, S., Corthier, G., Ehrlich, S. D., Renault, P.
(1999). Survival, Physiology, and Lysis of Lactococcus lactis in the Digestive Tract. Appl. Environ. Microbiol.
65: 4881-4886
[Abstract]
[Full Text]
-
Wilson, C. L., Ouellette, A. J., Satchell, D. P., Ayabe, T., López-Boado, Y. S., Stratman, J. L., Hultgren, S. J., Matrisian, L. M., Parks, W. C.
(1999). Regulation of Intestinal -Defensin Activation by the Metalloproteinase Matrilysin in Innate Host Defense. Science
286: 113-117
[Abstract]
[Full Text]
-
Yount, N. Y., Yuan, J., Tarver, A., Castro, T., Diamond, G., Tran, P. A., Levy, J. N., McCullough, C., Cullor, J. S., Bevins, C. L., Selsted, M. E.
(1999). Cloning and Expression of Bovine Neutrophil beta -Defensins. BIOSYNTHETIC PROFILE DURING NEUTROPHILIC MATURATION AND LOCALIZATION OF MATURE PEPTIDE TO NOVEL CYTOPLASMIC DENSE GRANULES. J. Biol. Chem.
274: 26249-26258
[Abstract]
[Full Text]
-
Condon, M. R., Viera, A., D'Alessio, M., Diamond, G.
(1999). Induction of a Rat Enteric Defensin Gene by Hemorrhagic Shock. Infect. Immun.
67: 4787-4793
[Abstract]
[Full Text]
-
Shirafuji, Y., Oono, T., Kanzaki, H., Hirakawa, S., Arata, J.
(1999). Detection of Cryptdin in Mouse Skin. CVI
6: 336-340
[Abstract]
[Full Text]
-
Lillard, J. W. Jr., Boyaka, P. N., Chertov, O., Oppenheim, J. J., McGhee, J. R.
(1999). Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc. Natl. Acad. Sci. USA
96: 651-656
[Abstract]
[Full Text]
-
Rose, F. R. A. J., Bailey, K., Keyte, J. W., Chan, W. C., Greenwood, D., Mahida, Y. R.
(1998). Potential Role of Epithelial Cell-Derived Histone H1 Proteins in Innate Antimicrobial Defense in the Human Gastrointestinal Tract. Infect. Immun.
66: 3255-3263
[Abstract]
[Full Text]
-
Tarver, A. P., Clark, D. P., Diamond, G., Russell, J. P., Erdjument-Bromage, H., Tempst, P., Cohen, K. S., Jones, D. E., Sweeney, R. W., Wines, M., Hwang, S., Bevins, C. L.
(1998). Enteric beta -Defensin: Molecular Cloning and Characterization of a Gene with Inducible Intestinal Epithelial Cell Expression Associated with Cryptosporidium parvum Infection. Infect. Immun.
66: 1045-1056
[Abstract]
[Full Text]
-
Bals, R., Goldman, M. J., Wilson, J. M.
(1998). Mouse beta -Defensin 1 Is a Salt-Sensitive Antimicrobial Peptide Present in Epithelia of the Lung and Urogenital Tract. Infect. Immun.
66: 1225-1232
[Abstract]
[Full Text]
-
Mallow, E. B., Harris, A., Salzman, N., Russell, J. P., DeBerardinis, R. J., Ruchelli, E., Bevins, C. L.
(1996). Human Enteric Defensins. J. Biol. Chem.
271: 4038-4045
[Abstract]
[Full Text]
Copyright © 1992 by the American Society for Microbiology. All rights reserved.