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: 6387036
• 负责人: STEWART C WANG
• 金额: $ 23.38万
• 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/6387036
• 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.

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，而且是一种免疫器官， 引发协调的炎症反应炎症反应有助于 招募免疫细胞到伤口，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， 研究人员发现LBP具有高水平的生物活性， 在手术伤口中。低水平的LBP增强细胞因子的产生， 这些细胞因子在免疫细胞募集中至关重要， activation. LBP也是一种调理素，并增强LBP的杀菌活性。 杀菌/通透性增加蛋白（BPI）。伤口感染是 常见的热损伤后，并代表一个主要原因的发病率， mortality.虽然全身免疫反应可能有助于局部伤口 针对感染的反应，研究人员假设当地因素 在伤口中，特别是LBP，起着最关键的作用。他们 假设伤口内的LBP减少了细菌感染， 热损伤通过增加局部炎性细胞因子的产生， 杀菌活性研究人员建议通过以下方式来检验这一假设： 研究LBP、炎症细胞因子和 大鼠皮肤热损伤模型中白细胞细菌杀灭。LPS是 LPS也是最有效的诱导剂之一， 白细胞产生细胞因子，这种作用被显著放大， LBP。目的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 并且还将嗜中性粒细胞衍生的BPI的浓度降低了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增加将增加伤口杀菌 通过增强中性粒细胞和巨噬细胞的募集、激活和 杀菌目的2将确定伤口LBP对局部 热损伤后的杀菌活性。LBP存在于烧伤创面后， 伤害可能由多种来源引起， 血清和本地生产是最有可能的两种。伤口衍生的LBP将是 理想地处于调节局部免疫反应的位置， 损伤解决后，一旦改变毛细血管渗透性，作用就会增加。 目的3将确定创伤后LBP产生的来源和调节 热损伤