PULMONARY INTERSTITIAL FIBROSIS INDUCED BY HAPTENS

半抗原免疫性肺间质纤维化或HIPIF是一种治疗肺纤维化的新方法。 肺间质纤维化（PlF）的实验系统 在半抗原免疫动物的肺中的单一免疫攻击。 HIPIF系统是新颖的，并首次展示了 过敏接触等机制的可能性 皮炎可能导致肺部疾病。这些研究涉及 一个诱发肺病和皮肤病的环境毒素模型。我们 提出细胞介导的免疫机制诱导和 调节半抗原免疫和激发小鼠中的非消退性纤维化。的 观察到发展HIPIF的能力与 菌株对免疫半抗原的遗传反应能力， 将在小鼠中研究迟发型超敏反应。内 系统是仅挑战的对照组，代表肺损伤 纤维化模型。我们将确定影响 或促进免疫纤维化病变， 毒性对照（仅挑战）。响应的比较也将 在两个容量不相等的接触敏化剂之间进行 诱导纤维化（TNP>DNP）。淋巴细胞亚群的描述， 巨噬细胞和成纤维细胞，它们在各种 将进行小鼠的治疗组。将定义这些子集 通过细胞表面分子表型和细胞因子mRNA谱。不 将通过限度分析肺淋巴组织内的细胞 稀释分析以确定细胞毒性T细胞前体频率。中 努力研究T淋巴细胞反应和抗原的独特方面 在肺T细胞克隆和杂交瘤中呈现细胞特异性 将被生成。将使用功能和抗原测定来确定 相关生物活性和灌洗液中细胞因子的存在 和肺单核细胞亚群的培养上清液 在各种处理中从小鼠肺和肺门淋巴结收获 组抗体敲除研究将有助于确定 体内细胞因子。纤维化将通过以下量来定义： 羟脯氨酸（胶原蛋白），在体内和体外沉积 从处理组收获的成纤维细胞培养物以及 用胶原特异性染色进行形态学研究。仔细选择 每种范式中独特现象的分析将有助于剖析监管 免疫与毒性介导的肺纤维化的对比。以此来 研究环境毒素可能使用的机制（小 反应性化学物质）诱导肺间质纤维化 及其与迟发型超敏反应的关系 肺和皮肤。

The hapten immune pulmonary interstitial fibrosis or HIPIF is an experimental system for pulmonary interstitial fibrosis (PlF) induced by a single immunological challenge in the lungs of hapten-immune animals. The HIPIF system is novel and demonstrates, for the first time, the possibility that mechanisms such as those involved in allergic contact dermatitis may contribute to lung disease. Thus, these studies deal with a model for environmental toxins that induce lung and skin disease. We propose the hypothesis that cell mediated immune mechanisms induce and regulate non-resolving fibrosis in hapten-immune and challenged mice. The observation that the ability to develop HIPIF is associated with the genetic ability of the strain to respond to the immunizing hapten with a delayed type hypersensitivity response will be studied in mice. Within the system is a challenged-only control group that represents a lung injury model of fibrosis. We will determine the regulatory factors that influence or promote the immune fibrotic lesion as compared to the lesion seen in the toxic control (challenged-only). Comparisons of responses also will be made between two contact sensitizers which are not equal in their capacity to induce fibrosis (TNP>DNP). A description of the subsets of lymphocytes, macrophages, and fibroblasts that accumulate in the lungs of the various treatment groups of mice will be performed. These subsets will be defined both by cell surface molecular phenotype and by cytokine mRNA profile. T cells within the pulmonary lymphoid tissues will be analyzed by limit dilution analysis to determine cytotoxic T cell precursor frequency. In an effort to study unique aspects of T lymphocyte response and antigen presenting cell peculiarities within the lung T cell clones and hybridomas will be generated. Functional and antigenic assays will be used to define both associated bioactivities and presence of cytokines in lavage fluid and culture supernatants of subpopulations of lung mononuclear cells harvested from mouse lungs and hilar lymph nodes in the various treatment groups. Antibody knockout studies will help determine the role of cytokines in vivo. The fibrosis will be defined by the amount of hydroxyproline (collagen) that is deposited both in vivo and in vitro cultures of fibroblasts harvested from the treatment groups as well as with morphologic studies using collagen specific stains. Careful selection of unique phenomenon in each paradigm will help to dissect the regulation of immune versus toxic mediated pulmonary fibrosis. In this way, we will study the mechanism that might be used by environmental toxins (small reactive chemicals) in the induction of pulmonary interstitial fibrosis and their relationship to delayed type hypersensitivity responses in the lung as well as the skin.