BIOCHEMICAL RELATIONSHIPS OF BASOPHILS AND EOSINOPHILS

人嗜碱性粒细胞的发育和生化关系 嗜酸性粒细胞及其在过敏性，寄生性， 炎症和其他疾病尚不清楚。 嗜碱性粒细胞和嗜酸性粒细胞可能 从一个共同的祖先分化出来，某些可能的嗜酸性粒细胞 已经发现特定的膜和阳离子颗粒蛋白 嗜碱性粒细胞的成分，但不是中性粒细胞或肥大细胞。 一些 这些嗜酸性粒细胞颗粒衍生的阳离子蛋白刺激嗜碱性粒细胞， 肥大细胞释放炎症介质。 进一步阐明 个体发育，生物化学和人类功能的相互关联的方面 该研究将研究嗜碱性和嗜酸性白细胞：1） 比较定位，理化和生化特性， 这些粒细胞共有的蛋白质，2）比较生物合成， 翻译后加工和/或这些蛋白质被成熟的 外周血来源的细胞和分化过程中的未成熟细胞， 和3）细胞活化和细胞外的比较机制 分泌出它们共同的蛋白质。 这些研究将使用嗜碱性粒细胞， 嗜酸性粒细胞从外周血或特异性 人胎儿脐带血单个核细胞的诱导培养物，均质 纯化的嗜酸性粒细胞和嗜碱性粒细胞蛋白，以及 这些蛋白质。 亚细胞定位、酶促 Charcot-Leyden晶体蛋白的活性、摄取和分泌 （溶血磷脂酶），嗜酸性粒细胞颗粒主要碱性蛋白和嗜酸性粒细胞 嗜碱性粒细胞中的过氧化物酶将利用超微结构细胞化学， 放射自显影、免疫电镜和特异性 放射免疫测定 生物合成，翻译后加工， 这些蛋白质的分泌将通过代谢标记来研究 嗜碱性粒细胞和嗜酸性粒细胞在体外分化和成熟过程中 在诱导分化的胎儿脐带血单个核细胞培养物中， 嗜碱性粒细胞或嗜酸性粒细胞选择性生长因子。 此夕h 嗜酸性粒细胞过氧化物酶的细胞内活化以促进其自身 通过次氯酸-氯胺依赖性蛋白水解降解 机制，产生一些存在于和中的低Mr阳离子蛋白 将研究从嗜酸性粒细胞颗粒分泌的蛋白质。 这些研究 目的是提供一个更全面的了解骨髓， 嗜碱性粒细胞和嗜酸性粒细胞的生物化学和功能关系，以及 进一步确定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和相关免疫反应。

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.