Myeloperoxidase (MPO) released by activated neutrophils can initiate and promote host tissue damage. MPO produces hypochlorous acid (HOCl) that modifies chemical functional groups causing wholesale cellular damage and eventual death. A hierarchy of reactivity exists for HOCl, with sulfur-containing moieties amongst the most efficient scavengers, but other chemical moieties are lesser targets, including amines that form chloramine derivatives upon reaction with HOCl. Glutathione (GSH), the predominant non-protein thiol in eukaryotes and some prokaryotes, protects the cytosols of mammalian cells from damage by HOCl and other oxidants. It has been suggested that the inorganic sulfur-containing ion thiocyanate (SCN-) may serve a similar role as a sequestering agent of HOCl. Given the high reactivity of SCN- towards HOCl, a reaction that produces relatively benign hypothiocyanite (OSCN-), the presence of SCN- prevents HOCl-induced cell death of prokaryote and eukaryote cells. However, we demonstrate here that SCN- is also capable of resuscitating mammalian cells that have been subjected to otherwise lethal amounts of HOCl. At the molecular level, chloramines react with SCN- to produce OSCN-. At the protein level, SCN- returns function to key enzymes like glutathione reductase (a cysteine-active site enzyme that is responsible for maintaining GSH redox homeostasis) that have been damaged by HOCl. At the cellular level, chloramines are repaired and viability improved upon treatment of HOCl-damaged mammalian cells with SCN-. These results suggest perfusion of SCN containing physiological fluids to tissues that have been damaged by inflammatory response may be remedial.

Resuscitation of neutrophillic hypochlorous acid-induced damage of mammalian cells by thiocyanate

256th National Meeting (2018)

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