Debol S M, Herron M J, Nelson R D
Department of Microbiology, University of Minnesota Medical School, Minneapolis 55455-0392, USA.
J Leukoc Biol. 1997 Dec;62(6):827-36. doi: 10.1002/jlb.62.6.827.
Dapsone has clinical utility as an anti-inflammatory agent but the mechanism of this action remains unknown. We have previously reported that dapsone inhibits beta2 integrin (CD11b/CD18)-mediated adherence of human neutrophils in vitro and now describe studies designed to discover how dapsone-mediated inhibition of this neutrophil function occurs. Results indicate that dapsone interferes with the activation or function of the G-protein (Gi type) that initiates the signal transduction cascade common to chemotactic stimuli. They also show that dapsone-mediated suppression of this pathway inhibits the generation of second messengers essential to the activation of beta2 integrin molecules, as well as respiratory and secretory functions of neutrophils exposed to chemoattractants. We propose that the inhibition of chemoattractant-induced signal transduction by dapsone suppresses neutrophil recruitment and local production of toxic respiratory and secretory products in the affected skin of dermatitis herpetiformis and other neutrophilic dermatoses.
氨苯砜作为一种抗炎药具有临床效用，但其作用机制尚不清楚。我们之前报道过氨苯砜在体外可抑制人中性粒细胞的β2整合素（CD11b/CD18）介导的黏附，现在描述旨在发现氨苯砜介导的这种中性粒细胞功能抑制是如何发生的研究。结果表明，氨苯砜干扰了启动趋化刺激共同信号转导级联反应的G蛋白（Gi型）的激活或功能。结果还显示，氨苯砜介导的该途径抑制作用抑制了β2整合素分子激活所必需的第二信使的产生，以及暴露于趋化因子的中性粒细胞的呼吸和分泌功能。我们认为，氨苯砜对趋化因子诱导的信号转导的抑制作用可抑制疱疹样皮炎和其他嗜中性皮肤病受累皮肤中中性粒细胞的募集以及有毒呼吸和分泌产物的局部产生。
