Vogt R F, Dannenberg A M, Schofield B H, Hynes N A, Papirmeister B
Fundam Appl Toxicol. 1984 Apr;4(2 Pt 2):S71-83. doi: 10.1016/0272-0590(84)90139-8.
Sulfur mustard (SM) (di-2-chlorethyl sulfide), used for chemical warfare in World War I, is a highly reactive radiomimetic alkylating agent. When applied to the skin of rabbits and guinea pigs, it produced vascular leakage, leukocyte infiltration, and slow death of basal epidermal cells. Thirty to sixty minutes after exposure to SM, injury to the superficial microvasculature (beneath the SM application site) was detected by measuring vascular leakage with Evans blue dye and also with horseradish peroxidase. At this same time, injury to the superficial fibroblasts was observed ultrastructurally; and an unexpectedly high percentage of basophils was found among the early infiltrating granulocytes. At 2 to 4 hr, the vascular leakage ceased, and had resumed by 8 hr in a more diffuse form. At this time, the basal epidermal cells showed pyknotic nuclei, an increase in their lysosomal enzymes (observed histochemically), and autophagic vacuoles (observed ultrastructurally). Leukocyte infiltration was marked, consisting mostly of heterophils (PMN) with a reduced percentage of basophils. During the next 24 to 72 hr, the entire inflammatory reaction reached its peak; and a superficial, crust-covered ulcer developed. Then, over the next 10 days, the lesion gradually subsided with concomitant repair and healing. Glucocorticosteroids decreased the early edematous phase, but did not affect the rate of healing. These findings suggest that the skin response to sulfur mustard has an immediate and a delayed phase. The immediate phase, i.e., within the first hour, was characterized by injury to the superficial fibroblasts and to the endothelium of superficial capillaries and venules, possibly because of direct damage to their cell membranes. At this time, a restricted vascular leakage and a selective granulocyte infiltration containing many basophils occurred. The delayed phase, which became evident after 8 hr, was characterized by the death of basal epidermal cells, probably because of DNA damage. This phase was accompanied by generalized vascular leakage, by massive heterophil immigration, and eventually by ulceration.
硫芥（SM）（二氯乙基硫醚）在第一次世界大战中被用于化学战，是一种高反应性的拟辐射烷化剂。将其涂抹于兔和豚鼠的皮肤时，会导致血管渗漏、白细胞浸润以及基底表皮细胞缓慢死亡。接触硫芥30至60分钟后，通过用伊文思蓝染料以及辣根过氧化物酶测量血管渗漏，检测到浅表微脉管系统（硫芥涂抹部位下方）受到损伤。与此同时，超微结构观察发现浅表成纤维细胞受损；并且在早期浸润的粒细胞中发现嗜碱性粒细胞的比例出奇地高。2至4小时时，血管渗漏停止，8小时时以更弥漫的形式再次出现。此时，基底表皮细胞核固缩，其溶酶体酶增加（组织化学观察），并出现自噬空泡（超微结构观察）。白细胞浸润明显，主要由嗜中性粒细胞（PMN）组成，嗜碱性粒细胞比例降低。在接下来的24至72小时内，整个炎症反应达到高峰；并形成一个浅表的、覆盖痂皮的溃疡。然后，在接下来的10天里，病变随着修复和愈合逐渐消退。糖皮质激素可减轻早期水肿阶段，但不影响愈合速度。这些发现表明皮肤对硫芥的反应有即刻期和延迟期。即刻期，即最初一小时内，其特征是浅表成纤维细胞以及浅表毛细血管和小静脉内皮受损，可能是由于其细胞膜受到直接损伤。此时，出现局限性血管渗漏以及含有许多嗜碱性粒细胞的选择性粒细胞浸润。延迟期在8小时后变得明显，其特征是基底表皮细胞死亡，可能是由于DNA损伤。此阶段伴有全身性血管渗漏、大量嗜中性粒细胞移入，最终导致溃疡形成。
