Oxygen radical‐induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin

Natural killer (NK) cells are function- ally suppressed and induced to apoptosis by reac- tive oxygen species (ROS) produced by mononu- clear phagocytes (MPs). These inhibitory events are reversed by the biogenic amine serotonin. MPs generate hydrogen peroxide (H2O2), which is pro- cessed further by myeloperoxidase (MPO) to even more toxic compounds. Earlier studies suggest that serotonin scavenges MP-derived oxygen radicals generated by the MPO-H2O2 system. These find- ings led us to explore the capability of MPO-defi- cient MPs to induce NK cell dysfunction. We show that MPs recovered from subjects with MPO defi- ciency trigger inhibition of NK cells. In addition, MPs recovered from healthy subjects conveyed suppression of NK cells in the presence of the MPO inhibitor ceruloplasmin. We conclude that ROS- dependent inhibition of NK cell function is unre- stricted by the availability of MPO-derived oxygen radicals and that the protecting properties of sero- tonin may operate in the absence of functional MPO. Our data suggest a complex mechanism of MP-induced NK cell inhibition, which comprises the generation of interchangeable oxygen radicals. J. Leukoc. Biol. 75: 1111-1115; 2004.