NDLI: Characterization of Luminal Paneth Cell α-Defensins in Mouse Small Intestine ATTENUATED ANTIMICROBIAL ACTIVITIES OF PEPTIDES WITH TRUNCATED AMINO TERMINI

Content Provider	Journal of Biological Chemistry (JBC)
Author	Ouellette, Andre J. Satchell, Donald P. Hsieh, Matthew M. Hagen, Susan J. Selsted, Michael E.
Abstract	Paneth cells at the base of small intestinal crypts secrete apical granules that contain antimicrobial peptides including α-defensins, termed cryptdins. Using an antibody specific for mouse cryptdin-1, -2, -3, and -6, immunogold-localization studies demonstrated that cryptdins are constituents of mouse Paneth cell secretory granules. Several cryptdin peptides have been purified from rinses of adult mouse small intestine by gel filtration and reverse-phase high performance liquid chromatography. Their primary structures were determined by peptide sequencing, and their antimicrobial activities were compared with those of the corresponding tissue forms. The isolated luminal cryptdins included peptides identical to the tissue forms of cryptdin-2, -4, and -6 as well as variants of cryptdin-1, -4, and -6 that have N termini truncated by one or two residues. In assays of antimicrobial activity againstStaphylococcus aureus, Escherichia coli, and the defensin-sensitive Salmonella typhimurium phoP − mutant, full-length cryptdins had the same in vitro antibacterial activities whether isolated from tissue or from the lumen. In contrast, the N-terminal-truncated (des-Leu), (des-Leu-Arg)-cryptdin-6, and (des-Gly)-cryptdin-4 peptides were markedly less active. The microbicidal activities of recombinant cryptdin-4 and (des-Gly)-cryptdin-4 peptides against E. coli, and S. typhimurium showed that the N-terminal Gly residue or the length of the cryptdin-4 N terminus are determinants of microbicidal activity. Innate immunity in the crypt lumen may be modulated by aminopeptidase modification of α-defensins after peptide secretion.
Related Links	http://www.jbc.org/content/275/43/33969.abstract
Ending Page	33973
Starting Page	33969
Page Count	5
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	43
Volume Number	275
DOI	10.1074/jbc.M004062200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2000-10-27
Access Restriction	Open
Subject Keyword	Matrilysin (MMP-7) Piperazine-N,N′-bis(2-ethanesulfonic acid) (PIPES) Reverse-phase high performance liquid chromatography (RP-HPLC) Acid-urea polyacrylamide gel electrophoresis (AU-PAGE) Maltose-binding protein (MBP) Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF) PROTEIN SYNTHESIS POST-TRANSLATION MODIFICATION AND DEGRADATION
Alternative Title	Characterization of Luminal Paneth Cell α-Defensins in Mouse Small Intestine
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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