Human granulocytic ehrlichiosis agent inhibits superoxide anion generationby human neutrophils

The human granulocytic ehrlichiosis (HGE) agent, which replicates in neutro phils, was found not to induce superoxide anion (O-2(-)) generation or extr acellular release by human peripheral blood neutrophils, as measured by a l uminol-dependent chemiluminescence assay or a cytochrome c reduction assay, respectively. Furthermore, the HGE agent completely prevented O-2(-) relea se by neutrophils upon stimulation with phorbol myristate acetate (PMA), fo rmylmethionyl-leucyl-phenylalanine, or Escherichia coli. The inhibition was HGE agent dose dependent, required ehrlichial contact with the host cells, and was reversible upon removal of the extracellular HGE agent bound to th e host cells prior to PMA stimulation. Structural integrity of or new prote in synthesis by the HGE agent was not required for the inhibition; carbohyd rate but not surface protein of the HGE agent was required. The HGE agent d id not prevent O-2(-) generation in human peripheral blood monocytes derive d from the same individual. This neutrophil-specific prevention of O-2(-) g eneration by the HGE agent would be critical in survival of the HGE agent. This is the first demonstration of the rapid inhibition of preexisting NADP H oxidase in human neutrophils by the HGE agent.