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

不必要地延长粒细胞寿命和增强杀菌能力可能会产生有毒物质，如白三烯和超氧化物。中性粒细胞(PMN)的激活在全身炎症中起关键作用，如脓毒症和缺血再灌注损伤。细胞凋亡和有毒物质释放的调控被认为是抑制炎症性疾病和组织损伤的关键机制。例如，持续的呼吸道炎症被认为是哮喘的基本特征。组织学和支气管肺泡灌洗液(BAL)研究表明，即使在轻度哮喘患者的呼吸道中也存在炎性细胞浸润，并且在严重发作时这种细胞数量会增加。众所周知，哮喘急性发作期和哮喘突发致死性发作期患者的痰中，中性粒细胞往往比嗜酸性粒细胞更具优势，是主要的炎症细胞。中性粒细胞弹性蛋白酶(NE)存在于呼吸道上皮衬里的液体中，可进一步诱导炎症细胞因子(IL-8、GM-CSF)释放，破坏细胞外基质(ECM)结构。在体内，NE可被α间胰酶抑制剂(α_2巨球蛋白)迅速灭活。在这个过程中，α间胰酶抑制物被代谢成可检测到的血清胰酶抑制物，它也可能抑制NE的活性，从而形成一个动态平衡的负反馈环。我们推测STI在哮喘急性发作患者中可能更占优势。由于对哮喘患儿呼吸道炎症反应知之甚少，我们检测了哮喘急性发作期患儿血清中基质金属蛋白酶-2、组织基质金属蛋白酶-1、去甲肾上腺素和性激素水平。

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.