CYTOKINES AND ADHESION MOLECULES AND THERMAL INJURY

细胞因子和粘附分子与热损伤

基本信息

批准号：
2518987
负责人：
GERD O TILL
金额：
$ 17.49万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-09-01 至 1999-08-31
项目状态：
已结题

项目摘要

DESCRIPTION: (Adapted from the applicant's abstract) The pathophysiological mechanisms of local microvascular injury as well as secondary organ injury following thermal skin burns are not well understood. Neutrophils and vascular endothelial cells, together with inflammatory mediators and adhesion molecules, appear to play an important role in these events. It appears that local (skin) and remote (lung) injury after thermal trauma results from a complex interplay of cytokines (TNFa, IL-1), adhesion molecules (endothelial and leukocytic), and the complement activation products. It is postulated that cytokines play a major role in upregulation of both leukocytic and endothelial adhesion molecules. In order to explore the roles of these molecules, the applicants will assess the extent to which cytokine blockade protects against skin and lung vascular injury after thermal trauma of skin, evaluate the roles of adhesion molecules, and determine if blocking of C5a is protective. Since cytokine release and complement activation occur after thermal trauma and products of both mediator systems can activate neutrophils, they will assess the upregulation of CD11b and CD18 and the down regulation of L-selectin on blood neutrophils, after thermal injury, as surrogates of intravascular activation of these cells. Protective interventions will be evaluated for their ability to prevent these changes reflective of intravascular activation of neutrophils. At the tissue level, they will monitor E- and P- selectins, and ICAM-1 in skin and lung tissue sections. The studies will also be extended to include human burn patients.

描述：（根据申请人的摘要进行了改编）局部微血管损伤的病理生理机制由于热皮肤燃烧后的次要器官损伤不是理解。中性粒细胞和血管内皮细胞一起伴有炎症介质和粘附分子，似乎在这些事件中的重要作用。看来本地（皮肤）和热创伤后的遥控（肺）受伤是由复合物引起的细胞因子（TNFA，IL-1）的相互作用，粘附分子（内皮和白细胞）和补体激活产物。这是假设细胞因子在上调中起主要作用白细胞和内皮粘附分子。为了探索这些分子的作用，申请人将评估细胞因子阻滞剂预防皮肤和肺的程度皮肤热创伤后的血管损伤，评估粘附分子，并确定C5A的阻塞是否具有保护性。由于细胞因子释放和补体激活发生在热量之后两个调解人系统的创伤和产物都可以激活中性粒细胞，他们将评估CD11b和CD18的上调以及下调热损伤后血液中性粒细胞上L-选择素的调节，作为这些细胞血管内激活的替代物。将评估保护性干预措施的能力防止这些变化反映了血管内激活中性粒细胞。在组织水平上，它们将监测E-和P- Selectins，以及皮肤和肺组织切片中的ICAM-1。研究还将扩展到包括人类烧伤患者。