Urocanic acid isomers do not modulate intracellular calcium and cyclic AMP in human natural killer cells

Abstract

Ultraviolet irradiation influences natural killer cell function both in vitro and in vivo. The postulated ultraviolet photoreceptor in the epidermis, urocanic acid, has been reported to depress the cytotoxic activity of human natural killer cells. Therefore, this study investigated whether this would occur through specific second messengers, using a radioimmunoassay for intracellular adenosine 3',5'-cyclic monophosphate (cAMP) and Fluo-3 staining plus flow cytometry for free calcium. Both isolated lymphocytes and enriched CD16+ cells were used. A combination of the trans- and cis-isomers of urocanic acid (200 microg/ml) induced cAMP in both CD16+ and CD16- cells, but individual, stereospecific effects were not demonstrable. Urocanic acid did not induce significant changes in calcium levels in lymphocytes, or natural killer cells alone or conjugated to K562 target cells. Evidently, the biochemistry of urocanic acid-mediated natural killer-cell modulation is complex, and the cellular receptor(s) and specific signal transduction pathway(s) mediating the biological effects of urocanic acid remain elusive.