IMMUNOLOGICAL ASPECTS OF HEMORRHAGE

出血的免疫学方面

• 批准号: 3292185
• 负责人: IRSHAD H CHAUDRY
• 金额: $ 23.14万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3292185
• 关键词: Kupffer's cell; T lymphocyte; antibody dependent killer cell; antigens; disease /disorder model; flow cytometry; hemorrhage; immunomodulators; immunosuppression; interleukin 1; laboratory mouse; leukocyte activation /transformation; lymphokines; macrophage

Sepsis continues to be the major complicating factor following injury leading to multiple organ failure and death. Although it is well known that severe accidental injury causes soft and solid tissue destruction resulting in immunodepression, there has not been any systematic investigation addressing the question whether hemorrhage per se, which occurs in conjunction with other accidental injuries as well as a separate pathophysiological entity, play any major role in producing the immunodepression. Moreover, there is no information available concerning the effects of adequate fluid resuscitation following hemorrhage on the immune function. Our hypothesis is that hemorrhage without any significant tissue trauma and even with adequate fluid resuscitation compromises cell-mediated immunity and predisposes to sepsis. Moreover, our hypothesis is that immunomodulation by certain agents (thymopentine, thympoietine, Tuftsin, ATP-MgCl2, interleukin-2 and gamma interferon) following hemorrhage would improve the immune response and decrease the subsequent susceptibility to sepsis. Our plans are to examine the effects of hemorrhage and resuscitation on cell-mediated immunity, lymphokine regulation and natural killer cell activity using a murine hemorrhage model. The mice will be bled to and maintained at different levels of blood pressure for various time periods followed by adequate resuscitation. The time course of immunological alterations will then be measured by studying both the T-cell and macrophage function in vitro. Since Kupffer cell phagocytic activity is known to be depressed after hemorrhage, we will measure both antigen presentation and expression of membrane interleukin-1. These parameters will also be measured in peritoneal macrophages and splenic adherent cells. Antigen presentation by the macrophages is critical for effective activation of T helper cells. Ia antigen expression of Kupffer cells, peritoneal macrophages and splenic adherent cells will also be whether the post-hemorrhage mice are more susceptible to sepsis as produced by cecal ligation and puncture and determine whether the susceptibility to sepsis following hemorrhage can be prevented by immunomodulating agents. Our objective is also to determine whether the stimulatory action of some of the immunostimulating agents is due to influx of Ca2+ into the lymphocytes.

脓毒症仍然是以下的主要复杂因素 损伤导致多器官衰竭和死亡。尽管它是 众所周知，严重的意外伤害会导致柔软和坚硬 组织破坏导致的免疫抑制，目前还没有 是否进行了系统的调查，以解决这个问题 出血本身，与其他疾病一起发生 意外伤害以及单独的病理生理实体， 在产生免疫抑制的过程中起到任何重要作用。 此外，目前还没有关于 失血后充分液体复苏对患者预后的影响 免疫功能。我们的假设是，没有出血 任何严重的组织创伤，即使有足够的液体 复苏会损害细胞免疫和 易患败血症。此外，我们的假设是 某些药物的免疫调节作用(胸腺五肽， 胸腺素、Tuftsin、三磷酸腺苷-氯化镁、白介素2和伽马 出血后服用干扰素可提高免疫力 反应并降低随后的败血症易感性。我们的 计划是检查出血和复苏的效果。 论细胞免疫、淋巴因子调节与自然 用小鼠出血模型检测杀伤细胞活性。老鼠 会流到不同程度的血液中并维持在不同的水平 在不同的时间段内有足够的压力 复苏。免疫学变化的时间进程将 然后通过研究T细胞和巨噬细胞来测量 在体外发挥作用。因为库普弗细胞的吞噬活性是已知的 对于失血后抑郁，我们会检测这两种抗原 膜白介素1的呈递和表达。这些 参数也将在腹膜巨噬细胞和 脾贴壁细胞。巨噬细胞的抗原提呈 是有效激活辅助性T细胞的关键。IA抗原 枯否细胞、腹腔巨噬细胞和脾的表达 贴壁细胞也将决定出血后小鼠是否 盲肠结扎和盲肠结扎更容易感染败血症 穿刺法测定脓毒症的易感性 继发性出血可以通过免疫调节来预防 探员们。我们的目标也是确定是否 一些免疫刺激剂的刺激作用是 由于Ca~(2+)进入淋巴细胞。