ADP ribosylation of human neutrophil peptide-1 regulates its biological properties.
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.
Paone
Gregorino
G
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.
Wada
Akihiro
A
Stevens
Linda A
LA
Matin
Abul
A
Hirayama
Toshiya
T
Levine
Rodney L
RL
Moss
Joel
J
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*
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