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.
Subject(s)
ADP Ribose Transferases/metabolism , Adenosine Diphosphate Ribose/metabolism , T-Lymphocytes/immunology , alpha-Defensins/metabolism , ADP Ribose Transferases/genetics , ADP Ribose Transferases/pharmacology , Animals , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Antigens, CD/immunology , Bronchoalveolar Lavage Fluid/chemistry , CD3 Complex/immunology , Cloning, Molecular , Escherichia coli/drug effects , GPI-Linked Proteins , Glycosylphosphatidylinositols/metabolism , Humans , Microbial Sensitivity Tests , Muscle, Skeletal/metabolism , Neutrophils/immunology , Neutrophils/physiology , Poly(ADP-ribose) Polymerases/metabolism , Rabbits , Smoking , alpha-Defensins/geneticsABSTRACT
Eczema of the palm and obstructive sleep apnea (OSA) are common disorders. Proinflammatory cytokines and cell adhesion molecules are elevated in both of these disorders. We describe an unusual patient with OSA who had recurrent free remission of dermatitis after treatment with continuous positive airway pressure. We speculate that the resolution of the patient's skin condition may reflect the effects of increased tissue oxygenation during sleep, reduced sleep fragmentation, and/or a reduction in sympathetic tone associated with successful sleep apnea treatment.
