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Functional priming of inflammatory cells and modulation of their apoptosis: significance of these events in children's diseases

炎症细胞的功能启动及其细胞凋亡的调节：这些事件在儿童疾病中的意义

基本信息

批准号：
12670738
负责人：
YASUI Kozo
金额：
$ 1.98万
依托单位：
Shinshu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

The unnecessary prolongation of granulocyte life and augmentation of bactericidal ability may produce toxic substances such as leukotrienes and superoxide. Activation of neutrophils ( PMN ) play key roles in systemic inflammation such as that associated with sepsis and ischemia-reperfusion injury. The regulation of cellular apoptosis and the release of toxic substances has been proposed as a key mechanism for the inhibition of inflammatory disease and tissue damage. For example, persistent inflammation in the airways is thought to be an essential feature of bronchial asthma. Histological and bronchoalveolar lavage ( BAL ) fluid studies have demonstrated that inflammatory cell infiltration exists in the airway even in cases of mild asthma, and that this cell population increases in number during severe attacks. It is well-known that neutrophils are frequently more dominant than eosinophils as the major inflammatory cells in sputa from asthmatic patients during acute exacerbation and from those with sudden onset fatal asthma attack. The presence of neutrophil elastase ( NE ) in fluids in the epithelial lining of the airway has been reported to induce further inflammatory cytokine release ( IL-8, GM CSF ) and destroy structures of the extracellular matrix ( ECM ). NE is quickly inactivated by inter- α -trypsin inhibitor ( α_2 macroglobulin ) in vivo. During this process, inter- α -trypsin inhibitor is metabolized to detectable serum trypsin inhibitor ( STI ), which could also potentially inhibit the activity of NE, thus forming a homeostatic negative feedback loop. We speculated that STI may be more dominant in patients with acute asthmatic exacerbation. Since little is known about inflammatory reactions in the airways in childhood asthma, we examined the serum levels of MMP-2, TIMP 1, NE and STI in children with acute asthma exacerbation.

粒细胞寿命的不必要延长和杀菌能力的增强可能产生毒性物质，如白三烯和超氧化物。中性粒细胞（PMN）的活化在全身性炎症如脓毒症和缺血再灌注损伤中起关键作用。细胞凋亡和毒性物质释放的调节已被认为是抑制炎性疾病和组织损伤的关键机制。例如，气道中的持续炎症被认为是支气管哮喘的基本特征。组织学和支气管肺泡灌洗液（BAL）研究表明，即使在轻度哮喘的情况下，气道中也存在炎性细胞浸润，并且在严重发作期间，这种细胞群的数量增加。众所周知，中性粒细胞在急性发作期哮喘患者和突发致命性哮喘发作的患者中作为主要炎性细胞常常比嗜酸性粒细胞更占优势。据报道，在气道上皮衬里的流体中存在中性粒细胞弹性蛋白酶（NE）会诱导进一步的炎性细胞因子释放（IL-8，GM CSF）并破坏细胞外基质（ECM）的结构。NE在体内可被α_2巨球蛋白（α_2 macroglobulin，α_2巨球蛋白）迅速灭活。在此过程中，α -胰蛋白酶间抑制剂被代谢为可检测的血清胰蛋白酶抑制剂（STI），STI也可潜在地抑制NE的活性，从而形成稳态负反馈回路。我们推测STI可能在哮喘急性发作患者中更占优势。由于对儿童哮喘气道炎症反应知之甚少，我们检测了哮喘急性发作患儿血清MMP-2、TIMP-1、NE和STI水平。