ARS | Publication request: Bovine neutrophil generation of extracellular superoxide is inhibited by cis-urocanic acid.

Submitted to: BARC Poster Day
Publication Type: Abstract Only
Publication Acceptance Date: March 15, 2007
Publication Date: April 25, 2007
Citation: Rinaldi, M., Moroni, P., Leino, L., Laihia, J., Paape, M.J., Bannerman, D.D. 2007. Bovine neutrophil generation of extracellular superoxide is inhibited by cis-urocanic acid [abstract]. BARC Poster Day.

Technical Abstract: Neutrophils play a fundamental role in the host innate immune response during mastitis and other bacterial-mediated diseases of cattle through their ability to phagocytose and kill bacteria. The ability of neutrophils to kill bacteria is mediated through the generation of reactive oxygen species (ROS). However, the extracellular release of ROS can be deleterious to the host. In diseases such as mastitis, which are accompanied by a large influx of neutrophils, the generation of large quantities of ROS by activated neutrophils may result in significant injury to the mammary epithelium. Cis-urocanic acid (cis-UCA), which is formed from the UV photoisomerization of the trans isoform found naturally in human and animal skin, is an immunosuppressive molecule with anti-inflammatory properties. Because of the potential therapeutic use that a molecule such as cis-UCA may have in blocking excessive respiratory burst activity that may be deleterious to the host, the ability of cis-UCA to inhibit bovine neutrophil production of ROS was studied. Since neutrophil generation of ROS is necessary for optimal neutrophil bactericidal activity, the effect of cis-UCA on bovine neutrophil phagocytosis and bacterial killing were also assayed. Cis-UCA dose-dependently inhibited the respiratory burst activity of bovine neutrophils as measured by luminol chemiluminescence. Using two distinct assays, it was established that cis-UCA inhibits the generation of extracellular superoxide. In contrast, cis-UCA had no effect on the generation of intracellular levels of superoxide or other ROS. At concentrations that inhibited generation of extracellular superoxide, bovine neutrophil phagocytosis and bacterial activity remained intact. Together, these data suggest that cis-UCA inhibits the tissue-damaging generation of extracellular ROS while preserving neutrophil bactericidal activity. Ongoing studies in our laboratory are evaluating the ability of this compound to reduce the severity of inflammation in vivo.