EFFECT OF VITAMIN A DEFICIENCY ON LEUKOCYTE FUNCTION

维生素 A 缺乏对白细胞功能的影响

• 批准号: 3265694
• 负责人: Sally S. Twining
• 金额: $ 12.79万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-05-01 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3265694
• 关键词: Pseudomonas aeruginosa; all trans retinol; cell biology; cell sorting; chemoattractants; disease /disorder model; electron microscopy; fluorescence; histochemistry /cytochemistry; keratitis; laboratory rat; microscopy; neutrophil; nutrition related tag; phagocytosis; retinoate; retinoids; vitamin A deficiency; vitamin therapy

Vitamin A deficiency is the leading cause of childhood blindness worldwide. With increasing deficiency the cornea becomes keratinized and is susceptible to corneal ulceration (keratomalacia). Vitamin A deficient children, because of an increased susceptibility to infections, have higher morbidity and mortality rates than their normal peers from the same geographical area. Understanding why the inflammatory process is abnormal is important in the treatment of a vitamin A deficient child. The long term goal of this project is to elucidate the effects of vitamin A deficiency on the inflammatory process in the cornea. This grant is directed towards the polymorphonuclear leukocyte, a major mediator of corneal inflammation. The specific aims are the following: 1) To determine the time course of the effects of vitamin A deficiency on corneal and in vitro tested polymorphonuclear leukocyte functions. 2) To determine the ability of in vitro added retinol, retinoic acid and retinal to restore in vitro tested polymorphonuclear leukocyte function. 3) To determine the effect of in vivo administered therapeutic doses of vitamin A on corneal and in vitro tested polymorphonuclear leukocyte function 1, 2, 8 and 16 days after administration. 4) To determine which reactions involved in polymorphonuclear leukocyte function are altered. The rat model of vitamin A deficiency will be used at early, mid and late deficiency. In vivo function will be tested using the corneal model of Pseudomonas keratitis with a strain of Pseudomonas aeruginosa chosen for its ability to induce a controlled polymorphonuclear leukocyte response. Peripheral PMNs will be characterized in vitro as to their number and maturity, stability in the resting and active states, ability to chemotax towards a stimulus, phagocytose, kill and digest bacteria under stimulated and non-stimulated conditions. Reactions and/or mechanism involved in PMN activation, killing, digestion and self-protection will be addressed. Light and electron microscopy, fluorescence cytoflow, enzymatic and cell biology techniques will be used.

维生素A缺乏症是全球儿童失明的主要原因。 随着缺乏症的增加，角膜变得角膜活化，是 易受角膜溃疡（角膜肌酸）。 维生素A不足 由于对感染的敏感性增加，儿童的患者的易感性更高 发病率和死亡率比正常同龄人的发病率和死亡率 地理区域。 了解为什么炎症过程异常 对于治疗维生素不足的孩子很重要。 该项目的长期目标是阐明维生素A的影响 角膜中炎症过程的缺乏。 这笔赠款是 针对多形核白细胞，是 角膜炎症。 具体目的是以下： 1）确定维生素A缺乏症的影响的时间过程 角膜和体外测试的多形核白细胞功能。 2）确定体外添加的视黄醇，视黄酸和 视网膜以恢复体外测试的多形核白细胞功能。 3）确定体内给药的治疗剂量的影响 维生素A在角膜和体外测试的多形核白细胞上 函数1、2、8和16天后。 4）确定哪些反应涉及多形核白细胞 功能已更改。 维生素A缺乏症的大鼠模型将在早期，中期和晚期使用 不足。 体内功能将使用角膜模型进行测试 假单胞菌角膜炎与选择的铜绿假单胞菌菌株 它诱导受控的多形核白细胞反应的能力。 外围PMN将在体外表征其数量和 成熟度，静止状态和活性状态的稳定性，趋化能力 刺激下的刺激，吞噬，杀死和消化细菌 和未刺激的条件。 PMN涉及的反应和/或机制 将解决激活，杀戮，消化和自我保护。 光和电子显微镜，荧光细胞，酶和细胞 将使用生物学技术。