Inhibition of neutrophil adherence to antibody by dapsone: a possible therapeutic mechanism of dapsone in the treatment of IgA dermatoses.
Inhibition of neutrophil adherence to antibody by dapsone: a possible therapeutic mechanism of dapsone in the treatment of IgA dermatoses.
复制标题
氨苯砜抑制中性粒细胞对抗体的粘附：氨苯砜治疗 IgA 皮肤病的可能机制。
DOI：
10.1111/1523-1747.ep12471811
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Zone,JJ
中科院分区：
文献类型：
--
作者：
Thuong-Nguyen,V;Kadunce,DP;Hendrix,JD;Gammon,WR;Zone,JJ
氨苯砜在以抗体沉积和中性粒细胞积聚为特征的皮肤病中经常有效。我们假设氨苯砜的这种作用机制可能涉及抑制中性粒细胞对抗体的粘附。中性粒细胞粘附试验（测定皮肤切片上中性粒细胞与基底膜区结合抗体的结合）用于评价氨苯砜对中性粒细胞粘附免疫球蛋白A和免疫球蛋白G的影响。我们分别评价氨苯砜对线性免疫球蛋白A大疱性皮肤病和大疱性类天疱疮患者血清中正常中性粒细胞粘附免疫球蛋白A和免疫球蛋白G的影响。线性免疫球蛋白A大疱性皮肤病或大疱性类天疱疮抗体结合到正常皮肤切片的基底膜区，作为中性粒细胞粘附试验的底物。将氨苯砜直接添加到中性粒细胞或抗体源中，浓度为0 ~ 50 μg/ml（药理学范围）。在中性粒细胞中添加氨苯砜，在50 μg/ml时，对中性粒细胞粘附的抑制作用可达75%。当将氨苯砜直接添加到抗体本身时产生类似的抑制作用，尽管在中性粒细胞粘附试验中使用之前进行了清洗。对照标本包括患者血清的不相关部分未能显示出结合。与未接受治疗的患者相比，接受氨苯砜治疗的患者血清也显示出对中性粒细胞粘附的抑制。我们得出结论，氨苯砜以剂量依赖的方式抑制中性粒细胞对基底膜带抗体的粘附。这可能与对抗体的直接作用有关。这种抑制作用可能有助于氨砜治疗抗体介导疾病的临床疗效。
Dapsone is frequently effective in cutaneous diseases characterized by antibody deposition and accumulation of neutrophils. We hypothesized that this mechanism of action of dapsone may involve the inhibition of neutrophil adherence to antibody. the neutrophil adherence assay, which measures the binding of neutrophils to basement membrane zone-bound antibody on skin sections, was used to evaluate the effect of dapsone on neutrophil adherence to immunoglobulin A and immunoglobulin G. We evaluated the effect of dapsone on adherence of normal neutrophils to immunoglobulin A and immunoglobulin G from sera of linear immunoglobulin A bullous dermatosis and bullous pemphigoid patients, respectively. Linear immunoglobulin A bullous dermatosis or bullous pemphigoid antibody were bound to the basement membrane zone of normal skin sections as a substrate for the neutrophil adherence assay. Dapsone was added directly to the neutrophils or to the antibody source in concentrations of 0-50 μg/ml (pharmacologic range). Addition of dapsone to neutrophils produced an incremental inhibition of neutrophil adherence up to 75% at 50 μg/ml. Dapsone produced similar inhibition when added directly to the antibody itself, despite washing prior to usage in the neutrophil-adherence assay. Control specimens including irrelevant fractions of patient sera failed to demonstrate binding. Serum from a patient on dapsone therapy also showed inhibition of neutrophil adherence compared to the same patient on no therapy. We conclude that dapsone inhibits the adherence of neutrophils to basement membrane zone antibody in a dose-dependent manner. This may be related to an effect directly on antibody. This inhibition may contribute to the clinical efficacy of dapsone in antibody-mediated diseases.