Inflammatory cell recruitment in acute injury

描述（申请人提供）炎症细胞的募集， 包括巨噬细胞和嗜中性粒细胞，被认为是 伤口愈合中性粒细胞和/或巨噬细胞水平的改变已被 描述了许多创伤愈合受损的情况，包括老化， 糖尿病和全身性感染。这一广泛而长期的目标 建议是了解白细胞募集到损伤部位是如何 监管.本申请的假设是， 白细胞募集的调节对于最佳伤口愈合是关键的。我们 先前的研究已经表明白细胞浸润到愈合的伤口中 由相关白细胞化学引诱物家族的产生所控制 细胞因子，称为趋化因子。具体目标1采用了一种特征良好的 切除伤口愈合的小鼠模型，以确定 40到60个已知的趋化因子网络成员。有限微阵列分析 将用于将趋化因子簇的表达与 这是该伤口模型中炎症的特征性模式。这些数据将 在具体目标2中使用，这将确定基本和具体的 指定趋化因子在伤口愈合中的作用。的重要性 鉴定的趋化因子对中性粒细胞和巨噬细胞的募集将是 使用中和抗体检查。其他实验将 发现趋化因子表达的改变是否在受损的 治愈，如衰老。由于中性粒细胞募集对 伤口的修复只有最低限度的理解，具体目标3将测试 假设适当的中性粒细胞浸润影响愈合过程。 趋化因子的产生、炎症和增殖过程将是 与正常小鼠的伤口进行比较。总的来说，结果将 提供了关于1）趋化因子产生和炎症的新信息 伤口中的细胞募集，和2）异常伤口炎症在 伤口愈合受损建议的研究不仅适用于伤口 愈合，但更普遍的是急性炎症反应。这些知识 可能为病理性的 炎症和异常伤口修复。

Description (provided by applicant) The recruitment of inflammatory cells, including macrophages and neutrophils, is appreciated as an important part of wound healing. Altered levels of neutrophils and/or macrophages have been described in many circumstances of impaired wound healing, including aging, diabetes, and systemic infection. The broad, long-term objective of this proposal is to understand how leukocyte recruitment into sites of injury is regulated. The hypothesis of this application is that the temporal and spatial regulation of leukocyte recruitment is critical to optimal wound healing. Our previous studies have shown that leukocyte infiltration into healing wounds is governed by the production of a family of related leukocyte chemoattractant cytokines, termed chemokines. Specific Aim 1 employs a well-characterized murine model of excisional wound healing to define the expression patterns of 40 to 60 known members of the chemokine network. Limited microarray analysis will be used to correlate the expression of clusters of chemokines with the characterized pattern of inflammation in this wound model. This data will be utilized in Specific Aim 2, which will determine the essential and specific roles of designated chemokines in wound healing. The importance of the identified chemokines to the recruitment of neutrophils and macrophages will be examined utilizing neutralizing antibodies. Additional experiments will discover if alterations in the expression of chemokines play a role in impaired healing, such as aging. Since the importance of neutrophil recruitment to the repair of wounds is only minimally understood, Specific Aim 3 will test the hypothesis that proper neutrophil infiltration influences the healing process. Chemokine production, inflammation, and proliferative processes will be compared in wounds of neutropenic and normal mice. Overall, the results will provide novel information regarding 1) chemokine production and inflammatory cell recruitment in wounds, and 2) the role of aberrant wound inflammation in impaired wound healing. The proposed studies are applicable not only to wound healing, but more generally to the acute inflamnmatory response. This knowledge may suggest new therapeutic approaches for situations of pathologic inflammation and aberrant wound repair.