Redox Buffering of Physiologic Fluids by Inorganic Compounds: Neutrophils, which comprise 33-75% of all leukocytes in humans, possess an impressive armory of oxidative and non-oxidative mechanisms for combating microorganisms.  The oxidative defense mechanism of neutrophils is based upon NADPH oxidase and myeloperoxidase (MPO).  The NADPH oxidase system reduces molecular oxygen to generate reactive oxygen species (ROS) including H₂O₂.  In the presence of H₂O₂, MPO is capable of oxidizing all of the halides (except F^-), as well as the pseudohalide thiocyanate (SCN^-), to produce hypohalites that are many orders of magnitude more cytotoxic than H₂O₂ itself.  Hypohalites, and in particular hypochlorous acid (HOCl), appear to play a pivotal role in inflammation. When unchecked, neutrophil-induced inflammation results in local tissue damage, and MPO has been linked to numerous chronic diseases such as atherosclerosis, cystic fibrosis, and periodontitis. Since HOCl is an indiscriminant oxidant, whereas hypothiocyanite (OSCN^-) is only cytostatic toward eukaryotic cells, considerable attention has focused on the substrate selectivity of MPO.  We recently demonstrated that HOCl is capable of rapidly oxidizing SCN^- to give OSCN^-.  Thus, the non-enzymic transfer of oxidizing equivalents from HOCl to SCN^- substantiates the hypothesis that SCN^- can serve the role of a redox buffer, thereby governing the lifetime of the more powerful oxidant HOCl and its potential for host self-destruction.  This work has been published (Ashby, M. T.; Carlson, A. C.; Scott, M. J., J. Amer. Chem. Soc. 2004, 126, 15976-15977).  The model has been recent evidenced using “ultrafiltered” (sub-3 KDa) human blood plasma (Figure 1, unpublished results).

Acknowledgement:  We are very grateful to the American Heart Association (0555677Z), the Oklahoma Center for the Advancement of Science and Technology (HR02-019), and the Department of Education (GAANN) for their financial support of this project.