NHLBI CLINICAL INVESTIGATOR AWARD PROGRAM

人嗜碱性白细胞和肥大细胞具有明显的促炎作用 释放许多化学介质的细胞，包括组胺和 SRS-A，在涉及细胞交联性的免疫刺激后 表面结合的IgE分子。尽管已经进行了大量的研究 使用含有多种细胞类型的人肺实质碎片， 和啮齿动物细胞，详细的生化和免疫学研究还没有 是使用纯化的人类肥大细胞进行的。最近，我们有 开发了一种纯化人肺肥大细胞的技术 纯度大于95%的酶分散，离心法 逆流淋洗和免疫亲和层析。vbl.使用 这些细胞的纯化制剂，我们计划量化这些细胞的介体 这些细胞产生的炎症包括SRS-A、前列腺素和 溶酶体水解酶；花生四烯酸脂氧合酶产物的定量 由这些细胞产生的酸，并确定这些产物在 组胺释放；探索参与介质的生化机制 从这些细胞中释放；探索药物控制的方法 这些促炎细胞。这样的研究不仅承诺提供 关于人类细胞生物学和生物化学的重要信息 肺肥大细胞，还包括有关肺部疾病状态的信息，如 很可能是由于哮喘和慢性炎症性疾病， 至少在一定程度上，与炎症过程和炎症介质有关。

Human basophilic leukocytes and mast cells are markedly pro-inflammatory cells that release a number of chemical mediators, including histamine and SRS-A, after immunologic stimulation involving cross-linking of cell surface-bound IgE molecules. Although numerous studies have been performed using human lung parenchymal fragments containing a mixture of cell types, and rodent cells, detailed biochemical and immunologic studies have not been performed using purified human mast cells. Recently, we have developed a technique for the purification of human lung mast cells to purities of greater than 95% by enzymatic dispersion, centrifugation by countercurrent elutriation, and immunoaffinity chromatography. Using purified preparations of these cells, we plan to quantitate mediators of inflammation produced by these cells including SRS-A, prostaglandins, and lysosomal hydrolases; quantitate the lipoxygenase products of arachidonic acid produced by these cells and determine the role of these products in histamine release; explore biochemical mechanisms involved in mediator release from these cells; and explore methods for the pharmacologic control of these pro-inflammatory cells. Such studies promise not only to provide important information concerning the cell biology and biochemistry of human lung mast cells, but also information about pulmonary disease states such as bronchial asthma and chronic inflammatory disorders that are likely due, at least in part, to the inflammatory process and inflammatory mediators.