Harvath L, Yancey K B, Katz S I
J Immunol. 1986 Aug 15;137(4):1305-11.
The therapeutic efficacy of the sulfones, dapsone, and sulfoxone in neutrophilic dermatoses may be related to the effects of these drugs on neutrophil function. Therefore we determined whether neutrophil chemotactic migration to various chemoattractants could be inhibited by sulfones in vitro. The chemotactic responses of human neutrophils from healthy donors were tested by using N-formyl-methionyl-leucyl-phenylalanine (F-met-leu-phe), purified human C5a, and leukocyte-derived chemotactic factor (LDCF). Therapeutic concentrations of sulfones selectively inhibited neutrophil chemotaxis to F-met-leu-phe, but did not affect neutrophil chemotaxis to LDCF or C5a. Inhibition of neutrophil chemotaxis to F-met-leu-phe was induced by both dapsone and sulfoxone at a concentration of 10 micrograms/ml without affecting random migration, and the inhibition was reversed by washing the neutrophils. When dapsone- and sulfoxone-treated neutrophils (100 micrograms/ml) were stimulated with F-met-leu-phe, neutrophil superoxide generation was not inhibited. Sulfapyridine (10 micrograms/ml) also selectively inhibited neutrophil chemotaxis to F-met-leu-phe; however, sulfamethoxazole and sulfisoxazole did not affect chemotaxis. The inhibitory effects of dapsone, sulfoxone, and sulfapyridine could not be demonstrated with granulocytes from rabbits or guinea pigs nor with human monocytes. Experiments with radiolabeled dapsone showed rapid, nonspecific, and reversible binding of dapsone to human neutrophils. These data suggest that a mechanism of action of sulfones in neutrophilic dermatoses may be a selective inhibition of neutrophil migration to as yet undefined chemoattractants in the skin.
砜类药物、氨苯砜和舒砜那在嗜中性皮肤病中的治疗效果可能与这些药物对嗜中性粒细胞功能的影响有关。因此，我们测定了砜类药物在体外是否能够抑制嗜中性粒细胞向各种趋化因子的趋化性迁移。通过使用N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（F-甲硫-亮-苯丙）、纯化的人C5a和白细胞衍生趋化因子（LDCF），对健康供体的人嗜中性粒细胞的趋化反应进行了测试。砜类药物的治疗浓度选择性地抑制了嗜中性粒细胞对F-甲硫-亮-苯丙的趋化性，但不影响嗜中性粒细胞对LDCF或C5a的趋化性。氨苯砜和舒砜那在浓度为10微克/毫升时均可诱导对F-甲硫-亮-苯丙的嗜中性粒细胞趋化性抑制，且不影响随机迁移，通过洗涤嗜中性粒细胞可逆转这种抑制作用。当用F-甲硫-亮-苯丙刺激经氨苯砜和舒砜那处理的嗜中性粒细胞（100微克/毫升）时，嗜中性粒细胞超氧化物的生成未受抑制。磺胺吡啶（10微克/毫升）也选择性地抑制嗜中性粒细胞对F-甲硫-亮-苯丙的趋化性；然而，磺胺甲恶唑和磺胺异恶唑不影响趋化性。氨苯砜、舒砜那和磺胺吡啶的抑制作用在兔或豚鼠的粒细胞以及人单核细胞中均未得到证实。用放射性标记氨苯砜进行的实验表明，氨苯砜与人嗜中性粒细胞存在快速、非特异性且可逆的结合。这些数据表明，砜类药物在嗜中性皮肤病中的作用机制可能是选择性抑制嗜中性粒细胞向皮肤中尚未明确的趋化因子的迁移。
