title: ADP ribosylation of human neutrophil peptide-1 regulates its biological properties.
abstract: In human airways, epithelial cells lining the lumen and intraluminal cells (e.g., polymorphonuclear cells) participate in the innate immune response. These cells secrete or express on their surfaces arginine-specific ADP ribosyltransferases. Defensins, antimicrobial proteins secreted by immune cells, are arginine-rich, leading us to hypothesize that ADP ribosylation could modify their biological activities. We found that an arginine-specific ADP ribosyltransferase-1 present on airway epithelial cells modifies Arg-14 of alpha defensin-1. ADP-ribosylated defensin-1 had decreased antimicrobial and cytotoxic activities but still stimulated T cell chemotaxis and IL-8 release from A549 cells. Further, ADP-ribosylated defensin-1 inhibited cytotoxic and antimicrobial activities of unmodified defensin-1. We identified ADP-ribosylated defensin-1 in bronchoalveolar lavage fluid from smokers but not from nonsmokers, confirming its existence in vivo. Thus, airway mono-ADP-ribosyltransferases could have an important regulatory role in the innate immune response through modification of alpha defensin-1 and perhaps other basic molecules, with alteration of their biological properties.
authors.affiliation: Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Bldg 10 Rm 6D03, Bethesda, MD 20892-1590, USA.
authors.forename: Gregorino
authors.initials: G
authors.lastname: Paone
authors.forename: Akihiro
authors.initials: A
authors.lastname: Wada
authors.forename: Linda A
authors.initials: LA
authors.lastname: Stevens
authors.forename: Abul
authors.initials: A
authors.lastname: Matin
authors.forename: Toshiya
authors.initials: T
authors.lastname: Hirayama
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Levine
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D017252:CD3 Complex / Q000276:immunology; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000187:drug effects; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D018482:Muscle, Skeletal / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011817:Rabbits; D012907:Smoking; D013601:T-Lymphocytes / Q000276:immunology*; D023084:alpha-Defensins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015703:Antigens, CD; D017252:CD3 Complex; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases; D011065:Poly(ADP-ribose) Polymerases; C449301:ART1 protein, human