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Development and characterization of murine experimental autoimmune mastitis.

机译：小鼠实验性自身免疫性乳腺炎的发展和特征。

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摘要

Mastitis is a substantial clinical problem in lactating women that may result in severe pain and a failure of offspring to thrive. Many cases appear to involve no known infectious agent and as such may be fundamentally due to autoimmune mediated inflammation of the breast. The purpose of this study is to create a mouse model for autoimmune mastitis which would enable us to study the underlying basis of breast specific autoimmunity. To this end we have selected the milk specific protein, alpha-lactalbumin, as our targeted self antigen and generated recombinant alpha-lactalbumin for use as an immunogen.; Immunization of SWXJ mice with alpha-lactalbumin leads to a Th1/Tc1 proinflammatory response from CD4+/CD8+ T cells, respectively. Immunocytochemical analysis of mammary gland sections taken at various times from alpha-lactalbumin immunized mice show extensive T cell infiltration. Flow cytometry analysis of leukocytes taken from inflamed mammary glands show increased frequencies of CD4+ and CD8+ T cells expressing activated phenotype (CD44hi and CD45hi). In addition, quantitative RT-PCR analysis of breast tissue mRNA from alpha-lactalbumin immunized mice show significantly increased expression of inflammatory mediators including IFNgamma (P=0.010) and TNFalpha (P=0.057) but not IL-10 (P=0.14). Increased mammary mRNA expression of milk specific proteins such as alpha-lactalbumin (P=0.05) and alpha-casein (P=0.021) was also observed in lactating breast of EAM mice.; The phenotype of this targeted breast specific autoimmunity involves decreased ability to nurture offspring as evident from significantly inhibited growth curves (p=0.03) sometimes accompanied by kwashiorkor-like alopecia in litters from alpha-lactalbumin immunized females compared to control immunized females. Our data indicate that a targeted autoimmunity directed against alpha-lactalbumin leads to a breast-specific inflammation that compromises normal breast function and the ability of offspring to thrive. Our experimental model has useful applications for addressing complications in breast feeding as well as nutritionally based failure to thrive issues, and may also serve as a potent target immunogen for therapeutic breast cancer vaccination.*; *This dissertation is a compound document (contains both a paper copy and a CD as part of the dissertation). The CD requires the following system requirements: Adobe Acrobat.
机译：乳腺炎在哺乳期妇女中是一个严重的临床问题，可能导致严重的疼痛和后代无法成活。许多情况下似乎不涉及已知的传染原，因此从根本上讲可能是由于自身免疫介导的乳房炎症所致。这项研究的目的是创建一种自身免疫性乳腺炎的小鼠模型，这将使​​我们能够研究乳房特异性自身免疫性的基础。为此，我们选择了乳特异性蛋白α-乳白蛋白作为我们的靶向自身抗原，并生成了重组α-乳白蛋白用作免疫原。用α-乳白蛋白对SWXJ小鼠进行免疫分别导致CD4 + / CD8 + T细胞产生Th1 / Tc1促炎反应。从α-乳清蛋白免疫小鼠在不同时间采集的乳腺切片的免疫细胞化学分析显示广泛的T细胞浸润。取自发炎的乳腺的白细胞的流式细胞仪分析表明，表达活化表型（CD44hi和CD45hi）的CD4 +和CD8 + T细胞的频率增加。此外，对经α-乳白蛋白免疫的小鼠的乳腺组织mRNA进行定量RT-PCR分析显示，炎症介质的表达显着增加，包括IFNgamma（P = 0.010）和TNFalpha（P = 0.057），但IL-10则不然（P = 0.14）。在EAM小鼠的哺乳期乳汁中，还发现了乳特异性蛋白（如α-乳白蛋白（P = 0.05）和α-酪蛋白（P = 0.021））的乳腺mRNA表达增加。这种靶向的乳腺特异性自身免疫的表型涉及培育后代的能力下降，这明显受到抑制的生长曲线（p = 0.03）的明显体现，有时与接受免疫对照的雌性相比，接受α-乳清蛋白免疫的雌性幼仔中伴有kwashiorkor样脱发。我们的数据表明，针对α-乳白蛋白的靶向自身免疫可导致乳腺特异性炎症，从而损害正常的乳腺功能和后代spring壮成长的能力。我们的实验模型可用于解决母乳喂养中的并发症以及基于营养的繁琐问题，并且可以作为治疗性乳腺癌疫苗的有效靶点免疫原。 *本论文是复合文件（作为论文的一部分，包含纸质副本和CD）。该CD需要满足以下系统要求：Adobe Acrobat。

著录项

  • 作者

    Kesaraju, Pavani.;

  • 作者单位

    Cleveland State University.;

  • 授予单位 Cleveland State University.;
  • 学科 Health Sciences Immunology.
  • 学位 Ph.D.
  • 年度 2007
  • 页码 83 p.
  • 总页数 83
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 预防医学、卫生学;
  • 关键词

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