King A J, Sundaram S, Cendoroglo M, Acheson D W, Keusch G T
Division of Nephrology, New England Medical Center, Boston, MA 02111, USA.
J Infect Dis. 1999 Feb;179(2):503-7. doi: 10.1086/314579.
The role of inflammatory cells in the pathogenesis of hemolytic-uremic syndrome induced by Shiga toxin (Stx)-producing Escherichia coli remains unclear. The hypothesis that Stx has direct effects on polymorphonuclear cell (PMN) viability and function was examined by measuring apoptosis, necrosis, phagocytosis, and spontaneous and phorbol myristate acetate (PMA)-stimulated production of reactive oxygen intermediates. PMN from 6 healthy persons were exposed to medium, Stx1 (0.01-100 ng/mL), or heat-inactivated Stx1 or Stx1 B subunit (100 ng/mL). Stx1 induced a prominent dose-dependent respiratory burst from PMN at doses as low as 0.01 ng/mL; they were less responsive to PMA stimulation and had reduced ability for phagocytosis. This dysfunction was not due to cell death, as the magnitude of apoptosis and necrosis of PMN treated with Stx1 (100 ng/mL) for 20 h was identical to that of medium control. These results suggest that Stx has direct effects on PMN that could contribute to tissue injury early in the disease.
炎症细胞在产志贺毒素（Stx）的大肠杆菌诱导的溶血尿毒综合征发病机制中的作用仍不清楚。通过测量细胞凋亡、坏死、吞噬作用以及活性氧中间体的自发产生和佛波酯肉豆蔻酸酯乙酸酯（PMA）刺激产生，研究了Stx对多形核细胞（PMN）活力和功能有直接影响这一假说。来自6名健康人的PMN暴露于培养基、Stx1（0.01 - 100 ng/mL）、热灭活的Stx1或Stx1 B亚基（100 ng/mL）。Stx1在低至0.01 ng/mL的剂量下就能诱导PMN产生显著的剂量依赖性呼吸爆发；它们对PMA刺激的反应较弱，吞噬能力降低。这种功能障碍并非由于细胞死亡，因为用Stx1（100 ng/mL）处理20小时的PMN的凋亡和坏死程度与培养基对照组相同。这些结果表明，Stx对PMN有直接影响，这可能在疾病早期导致组织损伤。
