EFFECT OF VITAMIN A DEFICIENCY ON LEUKOCYTE FUNCTION

维生素A缺乏症是全球儿童失明的主要原因。 随着缺乏程度的增加，角膜变得角质化， 易患角膜溃疡（角膜软化症）。 维生素A缺乏 由于儿童对感染的易感性增加， 发病率和死亡率比他们的正常同龄人从相同的 地理区域。 了解为什么炎症过程是异常的 对治疗维生素A缺乏的儿童很重要。 该项目的长期目标是阐明维生素A的作用 角膜炎症过程中的缺陷。 这笔赠款是 针对多形核白细胞，一种主要的介质， 角膜炎症 具体目标如下： 1)为了确定维生素A缺乏症对 角膜和体外测试的多形核白细胞功能。 2)为了测定体外添加的视黄醇、视黄酸和 以恢复体外测试的多形核白细胞功能。 3)为了确定体内施用治疗剂量的 维生素A对角膜和体外测试的多形核白细胞的影响 给药后1、2、8和16天发挥作用。 4)确定多形核白细胞增多症涉及哪些反应 功能被改变了。 本研究采用大鼠维生素A缺乏模型，分早、中、晚三个阶段进行 缺陷 体内功能将使用以下角膜模型进行测试： 选择铜绿假单胞菌菌株用于治疗假单胞菌角膜炎 其诱导受控的多形核白细胞反应的能力。 外周PMN将在体外表征其数量和 成熟度，在静息和活动状态下的稳定性， 对刺激物产生吞噬、杀灭和消化作用 无刺激条件下。 PMN中涉及的反应和/或机制 活化、杀灭、消化和自我保护将得到解决。 光学和电子显微镜，荧光细胞流，酶和细胞 将使用生物技术。

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.