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Infection and Immunity, March 2004, p. 1470-1478, Vol. 72, No. 3
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.3.1470-1478.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Paneth Cell -Defensins from Rhesus Macaque Small Intestine

Hiroki Tanabe,^1, Jun Yuan,¹ Melinda M. Zaragoza,² Satya Dandekar,^2,3 Agnes Henschen-Edman,⁴ Michael E. Selsted,^1,5 and Andre J. Ouellette^1,5*

Departments of Pathology,¹ Microbiology and Molecular Genetics, College of Medicine,⁵ Department of Molecular Biology and Biochemistry, School of Biological Sciences, University of California, Irvine, California 92697,⁴ Department of Microbiology and Immunology, School of Medicine,² California National Primate Research Center, University of California, Davis, California 95616³

Received 22 October 2003/ Returned for modification 6 November 2003/ Accepted 17 November 2003

Antimicrobial peptides are secreted by small intestinal Paneth cells as components of innate immunity. To investigate the role of -defensins in enteric host defenses in nonhuman primates, -defensin cDNAs were isolated, -defensin peptides were purified from rhesus macaque small bowel, and the bactericidal activities of the peptides were measured. Six rhesus enteric -defensin (RED) cDNAs, RED-1 to RED-6, were identified in a jejunum cDNA library; the deduced RED peptides exhibited extensive diversity relative to the primary structures of rhesus myeloid -defensins. RED-4 was purified from monkey jejunum, and N-terminal peptide sequencing of putative RED-4 peptides identified two N termini, RTCYCRTGR... and TCYCRTGRC...; these corresponded to alternative N termini for the RED-4 molecules, as deduced from their molecular masses and RED cDNAs. In situ hybridization experiments localized RED mRNAs exclusively to small intestinal Paneth cells. Recombinant RED-1 to RED-4 were purified to homogeneity and shown to be microbicidal in the low micromolar range (10 µg/ml) against gram-positive and gram-negative bacteria, with individual peptides exhibiting variable target cell specificities. Thus, compared to myeloid -defensins from rhesus macaques, enteric -defensin peptides are highly variable in both primary structure and activity. These studies should facilitate further analyses of the role of -defensins in primate enteric immunity.

Editor: F. C. Fang

Present address: Sano Hospital, 3-3-1-15 Suehiro, Asahikawa, Hokkaido 071-8133, Japan.

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