I类PI3Ks对中性粒细胞活化在急性肺损伤发病中的作用

中性粒细胞肺内的大量浸润是急性肺损伤的主要病理特征之一．它能清除病原微生物等有害物质而发挥保护肺组织的作用．但若中性粒细胞大量的肺内浸润和过度的活化则可损伤肺组织，此负面作用在急性肺损伤的发生和发展中有重要的意义；磷酸肌醇3激酶的信号转导途径在调节急性肺损伤患者中性粒细胞的细胞因子表达、呼吸爆发、趋化及凋亡有重要的作用。故了解其作用机制可能会从细胞分子水平为急性肺损伤的防治开辟新的途径。     

中性粒细胞弹性蛋白酶在急性肺损伤发病中的作用

急性肺损伤的发病机制尚不清楚，但中性粒细胞在肺部聚集并释弹性蛋白酶具有重要作用。中性粒细胞弹性蛋白酶能分解内皮细胞外基质，增加血管通透性，促进血浆蛋白和活性物质的外漏，引起非心源性肺水肿，为对抗其活性，可采取抗蛋白酶，抗氧化剂以及表面活性物质替代治疗等措施。     

中性粒细胞活化和上皮细胞凋亡在急性肺损伤发生中的作用

致病因子一方面诱导肺泡巨噬细胞和上皮细胞产生多种细胞因子和趋化因子,激活中性粒细胞并使其向损伤部位聚集,从而产生炎症因子的瀑布式反应;另一方面激活死亡受体通路Fas-FasL等诱发肺上二皮细胞凋亡,从而引起肺组织损伤.另外,Fas活化后可通过介导肺内炎症介质释放和中性粒细胞聚集进一步加重肺损伤.中性粒细胞活化和上皮细胞凋亡在急性肺损伤的发生过程中起重要作用.     

中性粒细胞在急性肺损伤中的作用

简介急性肺损伤与急性呼吸窘迫综合征中，中性粒细胞含量、凋亡及相应炎症介质或细胞因子水平变化，并探讨中性粒细胞与急性肺损伤发病的关系。     

中性粒细胞在急性肺损伤中的作用

简介急性肺损伤与急性呼吸窘迫综合征中,中性粒细胞含量、凋亡及相应炎症介质或细胞因子水平变化,并探讨中性粒细胞与急性肺损伤发病的关系。     

中性粒细胞弹性蛋白酶与急性肺损伤

中性粒细胞弹性蛋白酶除了具有有效的宿主防御生理功能外 ,目前还被认为是体内最具破坏力的酶类之一。新观点认为中性粒细胞弹性蛋白酶能够在炎症部位逃逸多种蛋白酶抑制剂的调控作用 ,导致肺的通透屏障功能破坏和促炎细胞因子的释放 ,从而引起典型的急性肺损伤。该文综述了中性粒细胞弹性蛋白酶的生理作用及其在急性肺损伤中的作用的研究进展 ,为治疗急性肺损伤提供新的思路。     

白细胞介素-17在急性肺损伤发病机制中的作用

目的:探讨白细胞介素-17(interleukin-17,IL-17)在急性肺损伤(acutelunginjury,ALI)发病过程中的作用。方法:通过静脉内注射油酸(oleicacid,OA)0.1mL/kg建立大鼠ALI模型,用逆转录聚合酶链反应方法检测肺组织内IL-17信使核糖核酸(mRNA)表达水平;用免疫组织化学方法检测肺组织内IL-17蛋白质表达水平;用酶联免疫吸附方法检测支气管肺泡灌洗液(bronchoalveolarlavagefluid,BALF)和肺组织匀浆中IL-17的表达水平;并检测动脉血氧分压(PaO2)、BALF细胞计数、蛋白测定和组织学半定量评分。结果:正常大鼠肺组织及BALF内IL-17低水平表达,主要表达于气道上皮细胞;静注OA后1h,2h和4h,其表达无明显变化;静注OA后6h,其表达显著上调(P<0.05),间质中阳性着色的单个核细胞明显增多。ALI6h组与对照组BALF中,IL-17的表达量与中性粒细胞百分比呈显著正相关(r=0.682,P<0.05)。结论:在OA致大鼠ALI模型中,IL-17表达的上调相对滞后于中性粒细胞聚集和低氧血症的出现,可能在相对晚的时相参与致病过程。     

中性粒细胞弹性蛋白酶与急性肺损伤

中性粒细胞弹性蛋白酶除了具有有效的宿主防御生理功能外，目前还被认为是体内最具破坏力的酶类之一。新观点认为中性粒细胞弹性蛋白酶能够在炎症部位逃逸多种蛋白酶抑制剂的调控作用，导致肺的通透屏障功能破坏和促炎细胞因子的释放，从而引起典型的急性肺损伤。该文综述了中性粒细胞弹性蛋白酶的生理作用及其在急性肺损伤中的作用的研究进展，为治疗急性肺损伤提供新的思路。     

急性胰腺炎肺损伤的发病机制与防治进展

急性胰腺炎经常伴有急性肺损伤,其发生、发展与中性粒细胞、炎症介质等密切相关。本文就近年来急性胰腺炎肺损伤的发病机制和防治进展等作一简要综述。     

Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury

Complement depletion with cobra venom factor (CVF) before coronary artery ligation has been previously shown to reduce subsequent ischemic myocardial tissue injury in the baboon; however, whether complement depletion after the initiation of acute myocardial ischemia affords similar myocardial preservation is not known. Both complement depletion with CVF or the administration of certain nonsteroidal anti-inflammatory drugs, including ibuprofen, are thought to decrease myocardial infarct size by reducing polymorphonuclear leukocytic (PMN) infiltration; nevertheless, complement activation also could alter tissue injury by PMN-independent actions. Thus, the relative effects of CVF administered after coronary artery ligation on the subsequent development of myocardial tissue injury were assessed in a baboon myocardial infarction model. The animals were randomized into three treatment groups (n = 6): either CVF (125 units/kg) or saline was given 30 minutes after coronary artery ligation, and ibuprofen (12.5 mg/kg) was administered 30 minutes and 4 hours after ligation. The extent of ischemic myocardial injury was assessed 24 hours later. Relative to saline-treated baboons, both CVF and ibuprofen reduced PMN infiltration (36 +/- 4 vs. 24 +/- 4 and 24 +/- 4 PMN/mm2, respectively; mean +/- SEM) and histological evidence of transmural myocardial infarction (100% vs. 47% and 53%, respectively) in electrocardiographically designated, expected infarct sites. In both saline- and ibuprofen-treated animals, there was extensive localization of C4, C3, and C5 in all infarct sites; in contrast, there was only C4 localization in the CVF-treated baboons. When expected infarct sites were assessed for creatine kinase content as an indicator of tissue injury, there was significantly less epicardial and endocardial creatine kinase depletion in the CVF-treated animals (31.7 +/- 5.6% and 39.3 +/- 4.8%) than in the saline-treated animals (54.1 +/- 5.4% and 59.0 +/- 4.7%; p = 0.012 and 0.011, respectively). The percent creatine kinase depletion in the ibuprofen-treated animals was intermediate between the two other groups. These results suggest that depletion of complement after coronary ligation has beneficial effects in reducing tissue injury that cannot be explained solely on the basis of reducing PMN infiltration into the ischemic myocardium.     

急性肺损伤发病机制的研究进展

急性肺损伤（ALI）是临床常见的急危重症,病死率高,多年来对其发病机制进行了大量的研究。随着失控的炎症反应引发多器官功能紊乱综合征理论的出现,对ALI的认识转向对炎症发生、调控的认识,参与炎症的炎症细胞和细胞因子则成为研究的热点,这些细胞和细胞因子、炎症介质构成了ALI炎症反应和免疫调节的“细胞网络”和“细胞因子网络”在其发病过程中发挥重要作用,本文将对近年来的研究做一综述。     

Autoantibody-mediated complement c3a receptor activation contributes to the pathogenesis of preeclampsia

Preeclampsia (PE) is a prevalent life-threatening hypertensive disorder of pregnancy associated with increased complement activation. However, the causative factors and pathogenic role of increased complement activation in PE are largely unidentified. Here we report that a circulating maternal autoantibody, the angiotensin II type 1 receptor agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, stimulates deposition of complement C3 in placentas and kidneys of pregnant mice via angiotensin II type 1 receptor activation. Next, we provide in vivo evidence that selectively interfering with C3a signaling by a complement C3a receptor-specific antagonist significantly reduces hypertension from 167±7 to 143±5 mm Hg and proteinuria from 223.5±7.5 to 78.8±14.0 μg of albumin per milligram creatinine (both P<0.05) in angiotensin II type 1 receptor agonistic autoantibody-injected pregnant mice. In addition, we demonstrated that complement C3a receptor antagonist significantly inhibited autoantibody-induced circulating soluble fms-like tyrosine kinase 1, a known antiangiogenic protein associated with PE, and reduced small placental size with impaired angiogenesis and intrauterine growth restriction. Similarly, in humans, we demonstrate that C3 deposition is significantly elevated in the placentas of preeclamptic patients compared with normotensive controls. Lastly, we show that complement C3a receptor activation is a key mechanism underlying autoantibody-induced soluble fms-like tyrosine kinase 1 secretion and decreased angiogenesis in cultured human villous explants. Overall, we provide mouse and human evidence that angiotensin II type 1 receptor agonistic autoantibody-mediated activation contributes to elevated C3 and that complement C3a receptor signaling is a key mechanism underlying the pathogenesis of the disease. These studies are the first to link angiotensin II type 1 receptor agonistic autoantibody with complement activation and to provide important new opportunities for therapeutic intervention in PE.     

Antibody-induced neutrophil activation as a trigger for transfusion-related acute lung injury in an ex vivo rat lung model

Transfusion-related acute lung injury (TRALI) is a hazardous complication of transfusion and has become the leading cause of transfusion-related death in the United States and United Kingdom. Although leukoagglutinating antibodies have been frequently shown to be associated with the syndrome, the mechanism by which they induce TRALI is poorly understood. Therefore, we reproduced TRALI in an ex vivo rat lung model. Our data demonstrate that TRALI induction by antileukocyte antibodies is dependent on the density of the cognate antigen but does not necessarily require leukoagglutinating properties of the antibody or the presence of complement proteins. Rather, antibody-mediated activation of neutrophils seems to initiate TRALI, a process that could be triggered by neutrophil stimulation with fMLP. Antibody-mediated neutrophil activation and subsequent release of reactive oxygen species may thus represent key events in the pathophysiologic cascade that leads to immune TRALI.