PHAGOCYTIC CELL FUNCTION

吞噬细胞功能

• 批准号: 3960456
• 负责人: J I GALLIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3960456
• 关键词: cell adhesion; chemotaxis; child (0-11); chronic granulomatous disease; cytochrome b; electron microscopy; granule; human subject; hyperglobulinemia; immunoglobulin E; inflammation; interferons; leukocyte disorder; membrane activity; monoclonal antibody; monocyte; myelogenous leukemia; neutrophil; phagocytes; phagocytic dysfunction; phagocytosis; superoxides; tumor antigens

The major objective of this project has been to study neutrophil function in health and disease. We have shown that a patient congenitally deficient in neutrophil specific granules has major abnormalities in neutrophil function. In normal neutrophils fmet-leu-phe receptors and C3bi receptors (CT3) are present in large amounts in an intracellular pool that cosediments with the specific granules from normal neutrophils on sucrose and Percoll gradients. These are translocated to the cell surface after activation of neurophils resulting in a three fold increase in fmet-leu-phe receptor and CR3. CR3 deficient patients' neutrophils have abnormal chemotaxis, adhesiveness and spreading. Studies comparing peripheral blood and experimental exudate cells in guinea pigs and in man it has shown that there is preferential loss of neutrophil specific granules in the exudate cells. In addition, exudate cells have incresed fmet-leu-phe and C3bi receptor expression. Cytochrome b, found in specific granules, is an important component of the electron transport chain essential for superoxide production. We have shown that neutrophil activation of the respiratory burst requires cytochrome b translocation from an intracellular compartment to the plasma membrane with activation by the calcium ionophore A23187 but not with activation by phorbol esters and fmet-leu-phe. Of 30 patients with chronic granulomatous disease, 11 had cytochrome b deficiency (10 were boys with an X-linked inheritance but interestingly one patient was a girl with probable autosomal recessive inheritance. In other studies of patients with hyper IgE syndrome (recurrent infections) we found that there is decrease catabolism of IgE in these patients.

该项目的主要目的是研究中性粒细胞的功能 健康和疾病。 我们已经证明一个先天性缺陷的病人 在中性粒细胞特异性颗粒中， 功能 在正常中性粒细胞中，fmet-leu-phe受体和C3 bi受体 (CT3)大量存在于细胞内， 与蔗糖上正常中性粒细胞的特异性颗粒共沉淀 Percoll Gradients的 这些细胞在细胞分裂后， 嗜神经细胞的活化导致FMET-Leu-Phe增加三倍 受体和CR 3。 CR 3缺陷患者的中性粒细胞异常 趋化性、趋化性和扩散性。 比较外周血 以及在豚鼠和人类身上的实验性渗出细胞， 渗出液中嗜中性粒细胞特异性颗粒优先丢失 细胞 此外，渗出液细胞的fmet-leu-phe和C3 bi增加， 受体表达 细胞色素B存在于特定的颗粒中，是一种 电子传递链的重要组成部分， 超氧化物生成 我们已经表明，中性粒细胞激活的 呼吸爆发需要细胞色素B从细胞内 通过钙离子载体活化的质膜区室 A23187，但不被佛波酯和fmet-leu-phe激活。 月30日 慢性肉芽肿性疾病患者中，11例为细胞色素B缺乏症 (10都是X染色体连锁遗传的男孩但有趣的是 是一个很可能是常染色体隐性遗传的女孩。 在其他研究中 高IgE综合征（复发性感染）患者中，我们发现， 这些患者的IgE水平降低。