Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
PLoS One. 2013 Sep 9;8(9):e74445. doi: 10.1371/journal.pone.0074445. eCollection 2013.
Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH)3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH)3 treatment of serum depletes complement components and activates the complement system. We show that complement activation by Al(OH)3 involves the three major pathways by monitoring complement components in Al(OH)3-treated serum and in Al(OH)3-containing precipitates. Al(OH)3 activation of complement results in deposition of C3 cleavage products and membrane attack complex (MAC) and in generation of the anaphylatoxins C3a and C5a. Complement activation was time dependent and inhibited by chelation with EDTA but not EGTA+Mg(2+). We thus confirm that Al(OH)3 activates the complement system and show that the alternative pathway is of major importance.
氢氧化铝是人类疫苗中最常用的佐剂,但它的作用模式仍知之甚少。在几项报告中都提出了补体参与氢氧化铝佐剂特性的问题,同时还存在一个“储存库效应”。在这里我们证实了氢氧化铝处理血清会消耗补体成分并激活补体系统。我们通过监测氢氧化铝处理血清和含有氢氧化铝沉淀中的补体成分,表明补体通过三条主要途径被氢氧化铝激活。氢氧化铝激活补体导致 C3 裂解产物和膜攻击复合物(MAC)的沉积,并产生过敏毒素 C3a 和 C5a。补体激活是时间依赖性的,可被 EDTA 螯合抑制,但不能被 EGTA+Mg(2+)抑制。因此,我们证实了氢氧化铝激活补体系统,并表明替代途径具有重要意义。