Paneth Cell α-Defensins from Rhesus Macaque Small Intestine

Hiroki Tanabe, Jun Yuan, Melinda M. Zaragoza, Satya Dandekar, Agnes Henschen-Edman, Michael E. Selsted, Andre J. Ouellette

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38 Scopus citations

Abstract

Antimicrobial peptides are secreted by small intestinal Paneth cells as components of innate immunity. To investigate the role of α-defensins in enteric host defenses in nonhuman primates, α-defensin cDNAs were isolated, α-defensin peptides were purified from rhesus macaque small bowel, and the bactericidal activities of the peptides were measured. Six rhesus enteric α-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 α-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 α-defensins from rhesus macaques, enteric α-defensin peptides are highly variable in both primary structure and activity. These studies should facilitate further analyses of the role of α-defensins in primate enteric immunity.

Original languageEnglish (US)
Pages (from-to)1470-1478
Number of pages9
JournalInfection and Immunity
Volume72
Issue number3
DOIs
StatePublished - Mar 2004

ASJC Scopus subject areas

  • Immunology

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    Tanabe, H., Yuan, J., Zaragoza, M. M., Dandekar, S., Henschen-Edman, A., Selsted, M. E., & Ouellette, A. J. (2004). Paneth Cell α-Defensins from Rhesus Macaque Small Intestine. Infection and Immunity, 72(3), 1470-1478. https://doi.org/10.1128/IAI.72.3.1470-1478.2004