EXPERIMENTAL STUDIES ON IMMUNE GLOMERULONEPHRITIS

这些研究涉及细胞内固有的 肾小球细胞和浸润性免疫细胞在免疫介导的 肾小球损伤 待检查的肾小球疾病模型包括 肾小球基底膜抗血清介导的肾小球肾炎， 通过免疫复合物的沉积。 基本实验方法 包括受损肾小球的酶分解成悬浮液 组成细胞（内源性和外源性），分离 特定细胞类型的细胞活性，以及它们在 短期和长期组织培养。 将特别强调 的贡献的居民广告浸润单核吞噬细胞。 将测定肾小球内巨噬细胞的特异性免疫 功能如抗原呈递、分泌或展示 白细胞介素-1与淋巴细胞趋化因子和花生四烯酸的分泌 酸性代谢物。 内源性肾小球细胞的培养物将被 测定它们调节单核细胞募集到 肾小球 将进一步评估系膜细胞和上皮细胞 调节巨噬细胞免疫反应性的能力。 的 第一个要检查的参数是Ia抗原的表达， 肾小球内和腹腔巨噬细胞在存在因子 由固有肾小球细胞分泌。 在平行研究中， 肾小球内和间质淋巴细胞将从免疫细胞中获得。 涉及大鼠对特定抗原预致敏的肾损害 以及随后将该抗原置于肾小球中。 的 淋巴细胞将通过单核抗体进行表型分类。 将评估它们的激活状态，由 抗原驱动的增殖及其免疫调节因子的释放 淋巴因子：白细胞介素-2、γ干扰素和单核细胞趋化性 因素 最后，体液和细胞免疫刺激对 将检查肾小球细胞的内在功能， 血管紧张素II受体的细胞表达作为模型系统， 化验。

The investigations concern the cellular interactions between intrinsic glomerular cells and infiltrating immune cells in immunologically mediated glomerular injury. Glomerular disease models to be examined include glomerulonephritis mediated by antisera to glomerular basement membrane and by deposition of immune complexes. The basic experimental approach consists of enzymatic disassociation of injured glomeruli into a suspension of constituent cells (both endogenous and exogenously derived), isolation of particular cell types, and the assay of their cellular activities in short-term and long-term tissue culture. Particular emphasis will be on the contributions of the resident ad infiltrating mononuclear phagocytes. Intraglomerular macrophages will be assayed for specifically immune functions such as antigen presentation, secretion or display of Interleukin-1, and secretion of lymphocyte chemoattractants and arachidonic acid metabolites. Cultures of endogenous glomerular cells are to be assayed for their capacity to regulate monocyte recruitment to the glomerulus. Mesangial cells and epithelial cells will be further evaluated for their ability to modulate the immunoreactivity of macrophages. The first parameter to be examined will be the expression of Ia antigens by intraglomerular and peritoneal macrophages in the presence of factors secreted by intrinsic glomerular cells. In parallel studies, intraglomerular and interstitial lymphocytes will be obtained from immune renal lesions involving pre-sensitization of rats to particular antigens and the subsequent placing of that antigen in the glomerulus. The lymphocytes will be phenotypically classified by mononuclear antibodies. They will be evaluated for their state of activation, as determined by antigen-driven proliferation and their release of the immunoregulatory lymphokines: Interleukin-2, gamma interferon, and monocyte chemotaxis factors. Finally, the effect of humoral and cellular immune stimuli on intrinsic glomerular cell function will be examined, with the mesangial cell expression of angiotensin II receptors as the model system to be assayed.