title: Rhesus macaque θ-defensin isoforms: expression, antimicrobial activities, and demonstration of a prominent role in neutrophil granule microbicidal activities.
abstract: Mammalian defensins are cationic, antimicrobial peptides that play a central role in innate immunity. The peptides are composed of three structural subfamilies: α-, β-, and θ-defensins. θ-defensins are macrocyclic octadecapeptides expressed only in Old World monkeys and orangutans and are produced by the pair-wise, head-to-tail splicing of nonapeptides derived from their respective precursors. The existence of three active θ-defensin genes predicts that six different RTDs (1-6) are produced in this species. In this study, we isolated and quantified RTDs 1-6 from the neutrophils of 10 rhesus monkeys. RTD-1 was the most abundant θ-defensin, constituting ~50% of the RTD content; total RTD content varied by as much as threefold between animals. All peptides tested were microbicidal at ∼1 μM concentrations. The contribution of θ-defensins to macaque neutrophil antimicrobial activity was assessed by analyzing the microbicidal properties of neutrophil granule extracts after neutralizing θ-defensin content with a specific antibody. θ-defensin neutralization markedly reduced microbicidal activities of the corresponding extracts. Macaque neutrophil granule extracts had significantly greater microbicidal activity than those of human neutrophils, which lack θ-defensins. Supplementation of human granule extracts with RTD-1 markedly increased the microbicidal activity of these preparations, further demonstrating a prominent microbicidal role for θ-defensins.
authors.affiliation: Department of Pathology & Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Prasad
authors.initials: P
authors.lastname: Tongaonkar
authors.forename: Patti
authors.initials: P
authors.lastname: Tran
authors.forename: Kevin
authors.initials: K
authors.lastname: Roberts
authors.forename: Justin
authors.initials: J
authors.lastname: Schaal
authors.forename: George
authors.initials: G
authors.lastname: Osapay
authors.forename: Dat
authors.initials: D
authors.lastname: Tran
authors.forename: André J
authors.initials: AJ
authors.lastname: Ouellette
authors.forename: Michael E
authors.initials: ME
authors.lastname: Selsted
mesh_terms: D000818:Animals; D001491:Basophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002457:Cell Extracts / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D023082:Defensins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
chemical_list: D002457:Cell Extracts; D023082:Defensins; D020033:Protein Isoforms; D011498:Protein Precursors; C450142:theta-defensin