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：皮肤是抵御恶劣环境的第一道防线。 皮肤不仅是机械屏障，也是免疫器官 建立协调的炎症反应。炎症反应有助于 将免疫细胞招募到伤口并遏制和杀死入侵 有机体。脂多糖结合蛋白（LBP）是一种有效的促进剂 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 可增强细胞因子的产生 对脂多糖的反应；这些细胞因子对于免疫细胞的募集至关重要 激活。 LBP 也是一种调理素，可增强杀菌活性 杀菌/通透性增加蛋白（BPI）。伤口感染是 热损伤后很常见，是发病的主要原因 死亡。尽管全身免疫反应可能导致局部伤口 针对感染的反应，研究人员假设当地因素 伤口内，尤其是腰痛，起着最关键的作用。他们 假设伤口内的 LBP 可减少术后细菌感染 通过增加局部炎症细胞因子的产生和 杀菌活性。研究人员建议通过以下方式检验这一假设 研究LBP与炎症细胞因子之间的关系 大鼠皮肤热损伤模型中白细胞细菌的杀伤作用。脂多糖是 总是存在于烧伤创面； LPS 也是最有效的诱导剂之一 白细胞产生细胞因子的作用，并且这种作用被显着放大 腰痛。目标 1 将确定伤口 LBP 对局部细胞因子产生的影响 热损伤后。 LBP 作为革兰氏阴性菌的调理素发挥作用 并将中性粒细胞衍生的 BPI 浓度降低 10,000 倍 杀死革兰氏阴性菌所必需的。调查人员预计 烧伤部位的 LBP 增加会增加伤口杀菌力 通过增强中性粒细胞和巨噬细胞的招募、激活和 细菌杀灭。目标 2 将确定伤口 LBP 对局部的影响 热损伤后的杀菌活性。烧伤创面中存在 LBP 伤害可能由多种来源引起，其中从 血清和本地生产是最有可能的两种。伤口衍生的 LBP 是 非常适合调节局部免疫反应，并可能发挥作用 一旦损伤解决后毛细血管通透性改变，其作用就会增强。 目标 3 将确定伤口 LBP 产生的来源和调节 热损伤。