IMMUNOLOGICAL ASPECTS OF HEMORRHAGE

出血的免疫学方面

• 批准号: 3292188
• 负责人: IRSHAD H CHAUDRY
• 金额: $ 19.38万
• 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/3292188
• 关键词: Kupffer's cell; T lymphocyte; antigens; disease /disorder model; flow cytometry; hemorrhage; immunomodulators; immunosuppression; interleukin 1; laboratory mouse; leukocyte activation /transformation; lymphokines; macrophage; natural killer cells

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.

脓毒症仍然是主要的并发症因素， 损伤导致多器官衰竭和死亡。 虽然 众所周知，严重的意外伤害会导致柔软和坚固 组织破坏导致免疫抑制，没有 是否有任何系统的调查， 出血本身，与其他 意外伤害以及单独的病理生理实体， 在产生免疫抑制中起主要作用。 此外，没有关于 出血后充分液体复苏对 免疫功能。 我们的假设是， 任何严重的组织创伤，即使有足够的液体 复苏损害细胞介导的免疫， 易患败血症 此外，我们的假设是， 通过某些试剂（胸腺嘧啶， 胸腺生成素、Tuftsin、ATP-MgCl 2、白细胞介素-2和γ 干扰素）出血后将提高免疫 反应和降低随后的易感性脓毒症。 我们 计划是检查出血和复苏的影响 对细胞介导的免疫、淋巴因子调节和自然 使用鼠出血模型的杀伤细胞活性。 小鼠 将被流血的并维持在不同的血液水平 压力持续不同的时间段， 复苏术 免疫学改变的时间过程将 然后通过研究T细胞和巨噬细胞 体外功能 由于已知枯否细胞吞噬活性 出血后抑郁，我们将测量两种抗原 膜白细胞介素-1的呈递和表达。 这些 还将在腹膜巨噬细胞中测量参数， 脾贴壁细胞 巨噬细胞的抗原呈递 是有效激活T辅助细胞的关键。 Ia抗原 枯否细胞、腹腔巨噬细胞和脾脏的表达 贴壁细胞也将是出血后小鼠是否 更容易感染盲肠结扎引起的脓毒症， 穿刺判断是否易感染脓毒症 可以通过免疫调节来预防继发性出血 剂. 我们的目标也是确定 某些免疫刺激剂的刺激作用 由于Ca 2+流入淋巴细胞。