Augmented Injury due to Autologous Inflammatory Attack

自体炎症发作导致损伤加重

• 批准号: 8332445
• 负责人: FRANCIS D MOORE
• 金额: $ 50万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8332445
• 关键词: Adverse effects; Animal Experiments; Antibodies; Antigens; Autologous; Binding; Burn injury; Complement; Complement Activation; Data; Development; Event; Financial Support; Funding Mechanisms; Human; Immune response; Immunoglobulin M; Inflammation; Inflammatory; Inflammatory Response; Injury; Link; Modeling; Mus; Necrosis; Reperfusion Injury; Shock; Staining method; Stains; System; Techniques; Therapeutic; Tissues; disability; injured; mast cell; novel; response; trauma centers; wound

This proposal represents a continuing highly integrated examination of the mechanism by which injured tissue elicits a response from the host and the harmful effects of this response. Data derived from our past studies of the antibody-complement-mast cell pro-inflammatory response system suggests that, in model reperfusion injuries and model burns, this linked system causes more tissue loss than the original insult itself. Accordingly, interference with antibody-binding or complement activation or mast cell activation has produced a diminution in the extent of final injury. Thus, we hypothesize that major injury is critically exacerbated by the autologous inflammatory response. We wish to understand, in detail, (1) the exact sequence from injury antigen expression to necrosis; (2) whether natural IgM is a critical component; (3) how murine injury might parallel events in human; and (4) how to synthesize these findings into an effective therapeutic strategy to reduce the adverse effects of human injury. The Trauma Center Core (Project 1) will provide administrative support for these projects as well as provide financial support for consistent animal experiments and development of novel murine stains. Project 2 and 4 propose to study common mechanisms shared by mice and humans. Project 3 seeks to discover the exact mechanism of mast cell activation and mast cell-dependent tissue loss. By this funding mechanism, we wish to efficiently, and by multiple techniques, arrive at specific therapy for reperfusion injury and thermal burns. Successful therapy both lessens the ensuing disability from the local wound and may lessen the systemic impact by reductions in shock and secondary injury in response to systemic inflammation.

这一建议代表了对受损组织激发宿主反应的机制以及这种反应的有害影响的持续高度综合的研究。来自我们过去对抗体-补体-肥大细胞促炎反应系统的研究的数据表明，在模型再灌注损伤和模型烧伤中，该关联系统比原始损伤本身引起更多的组织损失。因此，干扰抗体结合或补体活化或肥大细胞活化已导致最终损伤程度的降低。因此，我们假设严重的损伤是严重加剧了自体炎症反应。我们希望详细了解：（1）从损伤抗原表达到坏死的确切顺序;（2）天然IgM是否是关键组分;（3）小鼠损伤如何与人类事件平行;以及（4）如何将这些发现综合成有效的治疗策略以减少人类损伤的不良反应。 创伤中心核心（项目1）将为这些项目提供行政支持，并为一致的动物实验和新型小鼠菌株的开发提供财政支持。项目2和4提出研究小鼠和人类共有的共同机制。项目3旨在发现肥大细胞激活和肥大细胞依赖性组织丢失的确切机制。 通过这种资助机制，我们希望通过多种技术有效地达到再灌注损伤和热烧伤的特异性治疗。成功的治疗既可以减轻局部伤口的残疾，也可以通过减少休克和全身炎症引起的继发性损伤来减轻全身影响。

项目成果

Prevention of intestinal ischemia-reperfusion injury in humanized mice.

预防人道化小鼠中的肠道缺血再灌注损伤。

• DOI: 10.1016/j.surg.2016.03.001
• 发表时间: 2016-08
• 期刊: Surgery
• 影响因子: 3.8
• 作者: Sheu EG;Wakatsuki K;Oakes S;Carroll MC;Moore FD Jr
• 通讯作者: Moore FD Jr

Glucocorticoid receptor antagonism by mifepristone alters phosphocreatine breakdown during sepsis.

米非司酮的糖皮质激素受体拮抗作用改变了脓毒症期间磷酸肌酸的分解。

• DOI: 10.1001/archsurg.1996.01430230061011
• 发表时间: 1996
• 期刊: Archives of surgery (Chicago, Ill. : 1960)
• 作者: Mitsuo,T;Rounds,J;Prechek,D;Wilmore,DW;Jacobs,DO
• 通讯作者: Jacobs,DO

Inhibition of rat gut reperfusion injury with an agent developed for the mouse. Evidence that amplification of injury by innate immunity is conserved between two animal species.

使用为小鼠开发的药物抑制大鼠肠道再灌注损伤。

• DOI: 10.1152/ajpregu.00380.2009
• 发表时间: 2010
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Afnan,Jalil;Ahmadi-Yazdi,Cyrus;Sheu,EricG;Oakes,SeanM;MooreJr,FrancisD
• 通讯作者: MooreJr,FrancisD

Does endotoxin-activated complement alter myocellular sodium homeostasis during sepsis?

脓毒症期间内毒素激活的补体是否会改变肌细胞钠稳态？

• DOI: 10.1097/00005373-200205000-00022
• 发表时间: 2002
• 期刊: The Journal of trauma
• 作者: Wang,Weiyang;Okamoto,Ken;Jacobs,DannyO
• 通讯作者: Jacobs,DannyO

Cr supplementation decreases tyrosine phosphorylation of the CreaT in skeletal muscle during sepsis.

补充 Cr 会降低脓毒症期间骨骼肌中 CreaT 的酪氨酸磷酸化。

• DOI: 10.1152/ajpendo.00506.2001
• 发表时间: 2002
• 期刊: American journal of physiology. Endocrinology and metabolism.
• 作者: Wang,Weiyang;Jobst,MichaelA;Bell,Brian;Zhao,Chun-Rui;Shang,Li-Hong;Jacobs,DannyO
• 通讯作者: Jacobs,DannyO