WOUND RESPONSE TO INFECTION: ROLE OF LPS-BINDING PROTEIN

伤口对感染的反应：LPS 结合蛋白的作用

• 批准号: 6526185
• 负责人: STEWART C WANG
• 金额: $ 24.07万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6526185
• 关键词: binding proteins; burns; cytokine; enzyme linked immunosorbent assay; gram negative bacteria; host organism interaction; immunocytochemistry; inflammation; laboratory rat; lipopolysaccharides; protein structure function; western blottings; wound healing; wound infection

DESCRIPTION: Skin is the first line of defense against the hostile environment. Skin is not only a mechanical barrier but also an immune organ capable of mounting a coordinated inflammatory response. Inflammatory responses serve to recruit immune cells to the wound and also to contain and kill invading organisms. Lipopolysaccharide binding protein (LBP) is a potent facilitator of these functions and the investigators have found high levels of LBP bioactivity within surgical wounds. LBP at low levels potentiates cytokine production in response to LPS; these cytokines are critical in immune cell recruitment and activation. LBP is also an opsonin and potentiates the bactericidal activity of bactericidal/permeability increasing protein (BPI). Wound infections are commonplace after thermal injuries and represent a major cause of morbidity and mortality. Although systemic immune responses may contribute to local wound responses against infection, the investigators postulate that local factors within the wound, particularly LBP, play the most critical role. They hypothesize that LBP within the wound decreases bacterial infection after thermal injury by increasing local inflammatory cytokine production and bactericidal activity. The investigators propose to test this hypothesis by investigating the relationship between LBP, inflammatory cytokines and leukocyte bacterial killing in a rat model of cutaneous thermal injury. LPS is invariably present in burn wounds; LPS is also one of the most potent inducers of cytokine production by leukocytes and this action is markedly amplified by LBP. Aim 1 will determine the effect of wound LBP on local cytokine production after thermal injury. LBP functions as an opsonin for gram-negative bacteria and also reduces by 10,000-fold the concentration of neutrophil-derived BPI necessary to kill gram-negative bacteria. The investigators anticipate that increased LBP at the site of burn injury will increase wound bactericidal activity by potentiating neutrophil and macrophage recruitment, activation and bacterial killing. Aim 2 will determine the effect of wound LBP on local bactericidal activity after thermal injury. LBP present in the burn wound after injury could arise from a number of sources, of which transudation from the serum and local production are the two most likely. Wound derived LBP would be ideally situated to regulate the local immune response and may play an increasing role once altered capillary permeability after injury has resolved. Aim 3 will determine the source and regulation of wound LBP production after thermal injury.

描述：皮肤是针对敌对环境的第一道防线。 皮肤不仅是机械屏障，而且是能够的免疫器官 安装协调的炎症反应。炎症反应用于 将免疫细胞募集到伤口上，并遏制并杀死入侵 有机体。脂多糖结合蛋白（LBP）是有效的促进因子 这些功能和研究人员发现了高水平的LBP生物活性 在手术伤口内。低水平的LBP增强了细胞因子的产生 对LP的反应；这些细胞因子在免疫细胞募集和 激活。 LBP也是一个opsonin，增强了杀菌活性 杀菌/渗透性增加蛋白质（BPI）。伤口感染是 热损伤后常见，代表了发病率的主要原因 死亡。尽管系统性免疫反应可能会导致局部伤口 针对感染的反应，研究人员假设当地因素 在伤口（尤其是LBP）内，发挥了最关键的作用。他们 假设伤口内的LBP降低了细菌感染 通过增加局部炎症性细胞因子的产生和热损伤 杀菌活性。研究人员建议通过 研究LBP，炎症细胞因子和 皮肤热损伤大鼠模型中的白细胞细菌杀死。 LPS是 总是出现在烧伤伤口中； LPS也是最有效的诱因之一 白细胞产生细胞因子的作用，该作用显着放大 LBP。 AIM 1将确定伤口LBP对局部细胞因子产生的影响 热损伤后。 LBP充当革兰氏阴性细菌的opsonin 并且还减少了中性粒细胞衍生的BPI浓度的10,000倍 杀死革兰氏阴性细菌所必需的。调查人员预计 烧伤部位的LBP增加将增加伤口杀菌性 通过增强中性粒细胞和巨噬细胞募集，激活和 细菌杀死。 AIM 2将确定伤口LBP对局部的影响 热损伤后的杀菌活性。 LBP出现在烧伤中 受伤可能来自多种来源，其中来自 血清和局部生产最有可能。伤口派生的LBP将是 理想位置可以调节局部免疫反应，并可能发挥 一旦损伤后毛细血管渗透性的改变，就会提高作用。 AIM 3将确定伤口LBP产生的来源和调节 热损伤。