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

Betten, Åsa,1967Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin, Avdelningen för klinisk virologi,Institute of Laboratory Medicine, Dept of Clinical Virology (författare)

Natural killer (NK) cells are functionally suppressed and induced to apoptosis by reactive oxygen species (ROS) produced by mononuclear phagocytes (MPs). These inhibitory events are reversed by the biogenic amine serotonin. MPs generate hydrogen peroxide (H(2)O(2)), which is processed further by myeloperoxidase (MPO) to even more toxic compounds. Earlier studies suggest that serotonin scavenges MP-derived oxygen radicals generated by the MPO-H(2)O(2) system. These findings led us to explore the capability of MPO-deficient MPs to induce NK cell dysfunction. We show that MPs recovered from subjects with MPO deficiency 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 unrestricted by the availability of MPO-derived oxygen radicals and that the protecting properties of serotonin 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.

Dahlgren, Claes,1949Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för reumatologi och inflammationsforskning,Institute of Internal Medicine, Dept of Rheumatology and Inflammation Research(Swepub:gu)xdahcl (författare)
Mellqvist, Ulf-Henrik,1961Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine (författare)
Hermodsson, Svante,1934Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin, Avdelningen för klinisk virologi,Institute of Laboratory Medicine, Dept of Clinical Virology (författare)
Hellstrand, Kristoffer,1956Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin, Avdelningen för klinisk virologi,Institute of Laboratory Medicine, Dept of Clinical Virology(Swepub:gu)xhellk (författare)
Göteborgs universitetInstitutionen för laboratoriemedicin, Avdelningen för klinisk virologi (creator_code:org_t)

Av författaren/redakt...: Betten, Åsa, 196 ...; Dahlgren, Claes, ...; Mellqvist, Ulf-H ...; Hermodsson, Svan ...; Hellstrand, Kris ...

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