BIOCHEMICAL RELATIONSHIPS OF BASOPHILS AND EOSINOPHILS

人嗜碱性粒细胞的发育和生化关系 嗜酸性粒细胞及其功能相互作用在变态反应性，寄生性， 炎症性疾病和其他疾病尚不清楚。嗜碱性粒细胞和嗜酸性粒细胞可能 区别于普通的祖细胞和某些可能的嗜酸性粒细胞 已发现特定的膜和阳离子颗粒蛋白是 嗜碱性粒细胞的成分，但不包括中性粒细胞或肥大细胞。其中一些 这些嗜酸性粒细胞衍生的阳离子蛋白刺激嗜碱性粒细胞和 肥大细胞释放炎症介质。为了进一步澄清 人类个体发育、生物化学和功能的相互关联的方面 嗜碱性和嗜酸性白细胞，本研究将研究：1) 比较定位、理化和生化性质 这些粒细胞共有的蛋白质，2)相对生物合成， 翻译后加工，和/或成熟蛋白对这些蛋白质的摄取 外周血来源的细胞和分化过程中的未成熟细胞， 3)细胞激活和细胞外激活的比较机制 它们共同的蛋白质的分泌。这些研究将使用嗜碱性粒细胞和 从外周血或特定来源提纯的嗜酸性粒细胞 人胎儿脐带血单个核细胞的诱导培养 纯化的嗜酸性粒细胞和嗜碱性粒细胞蛋白及其单特异性抗血清 这些蛋白质。酶促亚细胞定位的研究 夏科-莱顿晶体蛋白的活性、摄取和分泌 (溶血磷脂酶)、嗜酸性粒细胞主要碱性蛋白和嗜酸性粒细胞 嗜碱性细胞中的过氧化物酶将利用超微结构细胞化学和 放射自显影、免疫电子显微镜和特异性 放射免疫分析。生物合成、翻译后加工和 这些蛋白质的分泌将通过代谢性标记来研究。 嗜碱性粒细胞和嗜酸性粒细胞在体外分化和成熟过程中的变化 脐血单个核细胞体外诱导分化的研究 有嗜碱性粒细胞或嗜酸性粒细胞选择性生长因子。此外， 细胞内激活嗜酸性粒细胞过氧化物酶以促进其自身 依赖次氯酸、氯胺的蛋白质降解 机制，以产生存在于和中的一些低MR阳离子蛋白 将对嗜酸性粒细胞颗粒分泌的物质进行调查。这些研究 目的是为了更全面地了解骨髓细胞， 嗜碱性粒细胞和嗜酸性粒细胞的生化和功能关系，以及 以进一步定义它们在嗜碱性粒细胞/肥大细胞中的动态相互作用 细胞-嗜酸性粒细胞轴在过敏及相关免疫反应中的作用。

The developmental and biochemical relationships of human basophils and eosinophils and their functional interactions in allergic, parasitic, inflammatory and other diseases are unclear. Basophils and eosinophils may differentiate from a common progenitor, and certain presumably eosinophil specific membrane and cationic granule proteins have been found to be constituents of basophils, but not of neutrophils or mast cells. Some of these eosinophil granule-derived cationic proteins stimulate basophils and mast cells to release mediators of inflammation. To further elucidate interrelated aspects of the ontogeny, biochemistry, and function of human basophilic and eosinophilic leukocytes, the research will study: 1) the comparative localization, and physicochemical and biochemical properties of proteins common to these granulocytes, 2) the comparative biosynthesis, post-translational processing, and/or uptake of these proteins by mature peripheral blood-derived cells and immature cells during differentiation, and 3) the comparative mechanisms for cell activation and extracellular secretion of their common proteins. These studies will use basophils and eosinophils purified both from peripheral blood or from specifically induced cultures of human fetal cord blood mononuclear cells, homogeneously purified eosinophil and basophil proteins, and monospecific antisera to these proteins. Studies of the subcellular localization, enzymatic activity, uptake and secretion of Charcot-Leyden crystal protein (lysophospholipase), eosinophil granule major basic protein and eosinophil peroxidase in the basophil will utilize ultrastructural cytochemistry and autoradiography, immunoelectron microscopy, and specific radioimmunoassays. The biosynthesis, post-translational processing, and secretion of these proteins will be studied by metabolically labeling them in basophils and eosinophils during in vitro differentiation and maturation in cultures of fetal cord blood mononuclear cells induced to differentiate with basophil or eosinophil selective growth factors. Further, the intracellular activation of eosinophil peroxidase to facilitate its own proteolytic degradation via a hypochlorous acid-, chloramine-dependent mechanism, to generate some of the low Mr cationic proteins present in and secreted from the eosinophil granule will be investigated. These studies aim to provide a more integrated understanding of the myelopoietic, biochemical, and functional relationships of basophils and eosinophils, and to further define their dynamic interactions in the basophil/mast cell-eosinophil axis in allergic and related immunologic responses.