Cloning and expression of bovine neutrophil β-defensins: Biosynthetic profile during neutrophilic maturation and localization of mature peptide to novel cytoplasmic dense granules

Nannette Y. Yount, Jun Yuan, Alan Tarver, Tammy Castro, Gill Diamond, Patti A. Tran, Jack N. Levy, Cheryl McCullough, James S Cullor, Charles L Bevins, Michael E. Selstedt

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

β-Defensins are microbicidal peptides implicated in host defense functions of phagocytic leukocytes and certain surface epithelial cells. Here we investigated the genetic structures and cellular expression of BNBD-4, - 12, and -13, three prototypic bovine neutrophil β-defensins. Characterization of the corresponding cDNAs indicated that BNBD-4 (41 residues) derives from a 63-amino acid prepropeptide and that BNBD-12 (38 residues) and BNBD-13 (42 residues) derive from a common 60-amino acid precursor (BNBD-12/13). The peptides were found to be encoded by two-exon genes that are closely related to bovine epithelial β-defensin genes. BNBD-4 and BNBD-12/13 mRNAs were most abundant in bone marrow, but were expressed differentially in certain non-myeloid tissues. In situ hybridization and immunohistochemical studies demonstrated that BNBD-4 synthesis is completed early in myelopoiesis. BNBD-12 was localized exclusively to the novel dense granules, organelles that also contain precursors of cathelicidins, antimicrobial peptides that undergo proteolytic processing during phagocytosis. In contrast to cathelicidins, Western blot analyses revealed that mature β-defensins are the predominant organellar form in myeloid cells. Stimulation of neutrophils with phorbol myristate acetate induced secretion of BNBD-12, indicating that it is co-secreted with pro- cathelicidins. The exocytosis of BNBD-12 by activated neutrophils reveals different mobilization pathways for myeloid α- and β-defensins.

Original languageEnglish (US)
Pages (from-to)26249-26258
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number37
DOIs
StatePublished - Sep 10 1999

ASJC Scopus subject areas

  • Biochemistry

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