Inflammatory cell recruitment in acute injury

描述(由申请人提供)炎性细胞的招募， 包括巨噬细胞和中性粒细胞，被认为是 伤口愈合。中性粒细胞和/或巨噬细胞水平的改变 在伤口愈合受损的许多情况下描述的，包括老化， 糖尿病和全身性感染。这样做的广泛、长期目标是 建议是了解白细胞如何重新聚集到损伤部位 受监管的。这个应用的假设是时间和空间 白细胞募集的调节是创面最佳愈合的关键。我们的 以前的研究表明，白细胞渗入愈合的伤口是 由一系列相关的白细胞趋化剂的产生所支配 细胞因子，称为趋化因子。特定目标1采用了一种很好的刻画 小鼠创面切除愈合模型以确定其表达模式 趋化因子网络的40到60个已知成员。有限微阵列分析 将被用来将趋化因子簇的表达与 在这个伤口模型中描述了炎症的模式。该数据将是 在具体目标2中使用，这将确定基本和具体目标 指定趋化因子在伤口愈合中的作用。重要的一点是 已确定的中性粒细胞和巨噬细胞募集的趋化因子将是 利用中和抗体进行检查。更多的实验将 发现趋化因子表达的改变是否在受损的患者中发挥作用 治愈，例如老化。由于中性粒细胞募集对 对伤口的修复只有最低限度的了解，具体目标3将考验 假设适当的中性粒细胞渗透会影响愈合过程。 趋化因子的产生、炎症和增殖过程 比较中性粒细胞减少症小鼠和正常小鼠的伤口。总体而言，结果将是 提供有关1)趋化因子产生和炎症的新信息 创面中的细胞募集，以及2)异常创面炎症在 伤口愈合受阻。拟议的研究不仅适用于创伤 治愈，但更普遍的是急性炎症反应。这一知识 可能会为病理情况提出新的治疗方法 炎症和异常的伤口修复。

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.