The Production of Congenital Malformations Using Tissue Antisera
The Production of Congenital Malformations Using Tissue Antisera
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使用组织抗血清产生先天性畸形
DOI：
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发表时间：
1966
期刊：
影响因子：
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通讯作者：
R. Brent
中科院分区：
文献类型：
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作者：
J. R. Bragonier;M. Frank;R. Brent
在一个畸形学模型系统中进行了研究，在该系统中，通过在妊娠第8天向妊娠大鼠注射羊抗大鼠肾抗血清，在后代中产生先天性畸形。为了确定抗血清是否仅通过与抗原结合产生其作用，或者是否需要免疫损伤的非特异性介质的直接参与，通过两种方法改变抗体分子的结构：（1）将抗血清的球蛋白级分还原并烷基化以解离IgM抗体并破坏IgG抗体的补体固定能力，和（2）用胃蛋白酶消化球蛋白级分以破坏IgG的Fc片段。这两个修改部分保留的能力，产生先天性畸形。这一结果表明，补体和其他非特异性介质不参与导致该系统畸形的免疫损伤。这一发现支持了这一主张，即这种致畸抗血清的作用，空间干扰正常卵黄囊功能在胎儿发育的关键时期。
Studies have been performed in a model teratologic system in which congenital malformations are produced in offspring by injecting sheep anti-rat kidney antiserum into pregnant rats on day 8 of gestation. To determine whether the antiserum produces its effects simply by combining with antigen, or whether direct participation of nonspecific mediators of immunologic damage is required, the antibody molecule was structurally altered by two methods: (1) a globulin fraction of the antiserum was reduced and alkylated to dissociate IgM antibody and destroy the complement-fixing ability of IgG antibody, and (2) a globulin fraction was digested with pepsin to destroy the Fc fragment of IgG. Both modified fractions retained the capacity to produce congenital malformations. This result suggests that complement and other nonspecific mediators are not involved in the immunologic damage which results in malformations in this system. The finding lends support to the proposition that this teratogenic antiserum acts by interfering sterically with normal yolk sac function during a critical period of fetal development.