REGULATION OF IGA PRODUCTION AND TRANSPORT BY VITAMIN A

最近的流行病学研究表明， 维生素A缺乏症（VAD）的风险增加， 呼吸道和肠道感染 分泌型伊加系统 在预防此类感染方面发挥重要作用。 VAD可 通过减少 伊加或损害其跨上皮表面的运输。 此类缺陷 这与维生素A的良好表征作用是一致的， 刺激和维持粘膜上皮细胞的分化 细胞和最近确定的调节抗体的作用， 生产 基于这些原因，我们建议研究 维生素A对BALB/c小鼠分泌型伊加反应的影响。 具体目标1 将确定VAD是否影响粘膜伊加反应和血清IgG 对甲型流感病毒鼻内感染或鼻内 用灭活病毒免疫。 以下实验将 进行：（A）总的和甲型流感特异性伊加的浓度 和IgG将通过ELISA测量（i）唾液，（ii）鼻咽， 分泌物，（iii）气管和支气管分泌物和（iv）血清 VAD和对照组小鼠。(B)浆细胞产生的数量 甲型流感特异性伊加和IgG将通过ELISPOT在 VAD小鼠和对照小鼠的呼吸道和脾脏。(C)的影响 VAD对防止再感染的保护作用将通过测量 上呼吸道和下呼吸道中的病毒复制（通过空斑试验） 先前感染或免疫的VAD和对照小鼠的道。 具体 目的2将确定聚合型伊加（pIgA）是否通过 多聚免疫球蛋白受体（pIgR）受维生素A状态的影响。 将进行以下实验：（A）肝细胞介导的 将静脉内施用的pIgA转运到胆汁中， 在VAD和对照小鼠中测量。(B)肝细胞pIgR蛋白水平将 通过蛋白质免疫印迹分析进行测量，并在VAD和 对照小鼠。(C)组织mRNA水平和转录速率的变化， 将使用单克隆抗体测量pIgR基因 溶液杂交（MASH）分析和核溢流分析， 分别在VAD和对照小鼠中。

Recent epidemiologic studies have shown that children with marginal vitamin A deficiency (VAD) are at increased risk of developing and dying from respiratory and enteric infections. The secretory IgA system plays an important role in protecting against such infections. VAD may increase susceptibility to mucosal infections by decreasing production of IgA or impairing its transport across epithelial surfaces. Such defects would be consistent both with vitamin A's well-characterized role in stimulating and maintaining the differentiation of mucosal epithelial cells and with its more recently identified role in regulating antibody production. For these reasons we propose to examine the effect of vitamin A on the secretory IgA response in BALB/c mice. Specific Aim 1 will determine if VAD affects the mucosal IgA response and serum IgG response to intranasal infection with influenza A virus or intranasal immunization with inactivated virus. The following experiments will be conducted: (A) The concentration of total and influenza A-specific IgA and IgG will be measured by ELISA in the (i) saliva, (ii) nasopharyngeal secretions, (iii) tracheal and bronchopulmonary secretions and (iv) serum of VAD and control mice. (B) The number of plasma cells producing influenza A-specific IgA and IgG will be enumerated by ELISPOT in the respiratory tract and spleen of VAD and control mice. (C) The effect of VAD on protection against reinfection will be determined by measuring virus replication (by plaque assay) in the upper and lower respiratory tract of previously infected or immunized VAD and control mice. Specific Aim 2 will determine if the transport of polymeric IgA (pIgA) via the polymeric immunoglobulin receptor (pIgR) is affected by vitamin A status. The following experiments will be conducted: (A) Hepatocyte-mediated transport of intravenously administered pIgA into the bile will be measured in VAD and control mice. (B) Hepatocyte pIgR protein levels will be measured by western immunoblot analysis and compared between VAD and control mice. (C) Tissue mRNA levels and the rate of transcription of the pIgR gene will be measured using the monoclonal-antibody solution-hybridization (MASH) assay and nuclear run-off assays, respectively, in VAD and control mice.