Mott J, Rikihisa Y
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210-1092, USA.
Infect Immun. 2000 Dec;68(12):6697-703. doi: 10.1128/IAI.68.12.6697-6703.2000.
The human granulocytic ehrlichiosis (HGE) agent, which replicates in neutrophils, was found not to induce superoxide anion (O(2)(-)) generation or extracellular release by human peripheral blood neutrophils, as measured by a luminol-dependent chemiluminescence assay or a cytochrome c reduction assay, respectively. Furthermore, the HGE agent completely prevented O(2-) release by neutrophils upon stimulation with phorbol myristate acetate (PMA), formylmethionyl-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 the host cells prior to PMA stimulation. Structural integrity of or new protein synthesis by the HGE agent was not required for the inhibition; carbohydrate but not surface protein of the HGE agent was required. The HGE agent did not prevent O(2-) generation in human peripheral blood monocytes derived from the same individual. This neutrophil-specific prevention of O(2-) generation by the HGE agent would be critical in survival of the HGE agent. This is the first demonstration of the rapid inhibition of preexisting NADPH oxidase in human neutrophils by the HGE agent.
人粒细胞埃立克体病（HGE）病原体在中性粒细胞中复制，通过鲁米诺依赖性化学发光测定法或细胞色素c还原测定法分别检测发现，它不会诱导人外周血中性粒细胞产生超氧阴离子（O₂⁻）或使其释放到细胞外。此外，HGE病原体在经佛波酯肉豆蔻酸乙酸酯（PMA）、甲酰甲硫氨酰亮氨酰苯丙氨酸或大肠杆菌刺激后，能完全阻止中性粒细胞释放O₂⁻。这种抑制作用呈HGE病原体剂量依赖性，需要埃立克体与宿主细胞接触，并且在PMA刺激前去除与宿主细胞结合的细胞外HGE病原体后是可逆的。HGE病原体的结构完整性或新蛋白质合成并非抑制作用所必需；HGE病原体的碳水化合物而非表面蛋白是必需的。HGE病原体不会阻止来自同一个体的人外周血单核细胞产生O₂⁻。HGE病原体对O₂⁻产生的这种中性粒细胞特异性抑制作用对HGE病原体的存活至关重要。这是首次证明HGE病原体能快速抑制人中性粒细胞中预先存在的NADPH氧化酶。
