Vavra Ashley K, Laurent Cecilia J, Ngo Vinh, Sweeney John F, Levitt Jonathan M
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, VAMC Building 110, Research Line 151, 2002 Holcombe Blvd., Houston, TX 77030, USA.
Int Immunopharmacol. 2004 Mar;4(3):437-45. doi: 10.1016/j.intimp.2004.01.021.
Sulfur mustard (2,2'-bis-chloroethyl-sulfide; SM) is a chemical warfare vesicant that causes debilitating skin lesions. Although a great deal of work has focused on the direct effects of SM exposure on the epithelium, it is unclear how much the inflammatory response, induced by exposure, contributes to lesion pathogenesis. Keratinocytes exposed to SM express a number of inflammatory mediators and elicit a cellular infiltrate consisting largely of polymorphonuclear leukocytes (PMN). PMN infiltration into SM lesions occurs as early as 30 min and peaks after several hours postexposure, and, despite the relatively short half-life of SM, PMN infiltrating a lesion could be exposed to micromolar concentrations of the agent. Previously, we have shown that exposure to low doses of sulfur mustard prime oxidative function in human PMN. The current study was undertaken to evaluate the effects of low-dose SM exposure on PMN phagocytosis, degranualtion and chemotaxis. PMN exposed to low doses of SM (50-200 microM) showed a dose-dependent enhancement of phagocytic function. Exocytosis of PMN azurophilic and specific granules [determined by analysis of granule-specific intravesicular receptors, Interleukin 10 receptor (IL-10R) and CD63] was also enhanced by SM exposure. Finally, we examined the effect of SM as a chemoattractant for PMN and show that SM is not itself a chemotaxin. These results suggest that SM injury may, in part, be caused by normal inflammatory function, and that therapeutic strategies aimed at down-regulating PMN activation could lessen the severity of SM injury and the time required for its resolution.
硫芥（2,2'-二氯乙基硫醚；SM）是一种化学战糜烂剂，可导致使人衰弱的皮肤损伤。尽管大量研究聚焦于硫芥暴露对上皮细胞的直接影响，但尚不清楚暴露引发的炎症反应在损伤发病机制中起多大作用。暴露于硫芥的角质形成细胞会表达多种炎症介质，并引发主要由多形核白细胞（PMN）组成的细胞浸润。PMN浸润到硫芥损伤部位最早在暴露后30分钟出现，并在暴露后数小时达到峰值，而且，尽管硫芥的半衰期相对较短，但浸润到损伤部位的PMN可能会接触到微摩尔浓度的该制剂。此前，我们已表明，低剂量硫芥暴露可启动人PMN的氧化功能。本研究旨在评估低剂量硫芥暴露对PMN吞噬作用、脱颗粒和趋化性的影响。暴露于低剂量硫芥（50 - 200微摩尔）的PMN显示出吞噬功能呈剂量依赖性增强。硫芥暴露还增强了PMN嗜苯胺蓝颗粒和特异性颗粒的胞吐作用[通过分析颗粒特异性囊泡内受体、白细胞介素10受体（IL - 10R）和CD63来确定]。最后，我们研究了硫芥作为PMN趋化剂的作用，结果表明硫芥本身不是趋化因子。这些结果表明，硫芥损伤可能部分是由正常炎症功能引起的，旨在下调PMN活化的治疗策略可能会减轻硫芥损伤的严重程度及其恢复所需的时间。
