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: 6650888
• 负责人: STEWART C WANG
• 金额: $ 24.79万
• 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 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650888
• 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。 皮肤不仅是一种机械屏障，而且是一个免疫器官，能够 进行协调一致的炎症反应。炎症反应有助于 将免疫细胞招募到伤口，也可以遏制和杀死入侵 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已经发现了高水平的LBP生物活性 在手术伤口内。低水平的LBP增强脑内细胞因子的产生 对内毒素的反应；这些细胞因子在免疫细胞募集和 激活。LBP也是一种调理素，可以增强其杀菌活性。 杀菌/通透性增加蛋白(BPI)。伤口感染是 在热损伤后很常见，是发病率和 死亡率。尽管全身免疫反应可能导致局部创伤 关于对感染的反应，研究人员假设当地因素 在伤口内，尤其是LBP起着最关键的作用。他们 假设伤口内的LBP可减少细菌感染 增加局部炎性细胞因子的产生和增加引起的热损伤 杀菌活性。研究人员建议通过以下方式来检验这一假设 探讨LBP、炎性细胞因子与肝纤维化的关系 皮肤烫伤大鼠模型中白细胞的细菌杀灭。LP是 总是存在于烧伤创面；内毒素也是最有效的诱因之一 白细胞产生细胞因子，这一作用被显著放大 伦敦金融城。目的1确定创伤LBP对局部细胞因子产生的影响 在热损伤后。LBP对革兰氏阴性菌的调理作用 并将中性粒细胞衍生的BPI浓度降低10,000倍 是杀死革兰氏阴性细菌所必需的。调查人员预计 烧伤部位LBP增加会增加创面杀菌作用 通过增强中性粒细胞和巨噬细胞的募集、激活和 细菌致死。目的2将确定创面LBP对局部的影响 热损伤后的杀菌活性。烧伤后创面中存在LBP 伤害可能由许多来源引起，其中来自于 血清和当地生产是最有可能的两种。伤口来源的LBP将是 处于调节局部免疫反应的理想位置，并可能起到 损伤后毛细血管通透性一旦改变，增加作用已消失。 目标3将确定伤口LBP产生的来源和调节 烫伤。

项目成果

Influence of lipopolysaccharide-binding protein on pulmonary inflammation in gram-negative pneumonia.

• DOI: 10.1097/shk.0000000000000349
• 发表时间: 2015-06
• 期刊: Shock (Augusta, Ga.)
• 作者: Taddonio MA;Dolgachev V;Bosmann M;Ward PA;Su G;Wang SC;Hemmila MR
• 通讯作者: Hemmila MR