Nitrite reduction by the red cell membrane: a mechanism with a biological role?

The possible role of nitric oxide (NO) metabolites in vivo has gained much interest in recent years, in particular, the interaction of these species with red blood cells. We investigated the potential for the membrane of red blood cells to act as a nitrite reductase site. Using both EPR (electromagnetic resonance spectroscopy) and ozone based chemiluminescence we were able to demonstrate NO generation from nitrite by the red cell membrane. The exact components responsible for this action are yet to be elucidated, but the response was unchanged by L-NMMA suggesting that eNOS is not involved. Reduction at the membrane could provide an entry route for NO into the red cell where it could produce potentially bioactive species e.g. nitrosylated proteins (RSNOs). If the nitrite reduction occurred on the outer surface of the red cell membrane it is also feasible that some NO may escape auto capture by that red cell, however in whole blood it is likely to be rapidly metabolised. In conclusion, this mechanism could provide a route by which nitrite, acting as a substrate, could be reduced to NO and form other, more biologically accessible species.