Witko-Sarsat V, Sermet-Gaudelus I, Lenoir G, Descamps-Latscha B
INSERM U507, Hôpital Necker Enfants-Malades, Paris, France.
Mediators Inflamm. 1999;8(1):7-11. doi: 10.1080/09629359990658.
The aim of this hypothesis is to provide new insights into the still unclear mechanisms governing airway inflammation in cystic fibrosis. Although the genetic basis of cystic fibrosis as well as the molecular structure of cystic fibrosis transmembrane regulator (CFTR), the mutated protein which causes the disease, have been well defined, a clear relationship between the genetic defect and the pulmonary pathophysiology, especially chronic infections and neutrophil-dominated airway inflammation has not been established. Cystic fibrosis is thus a unique pathological situation in that neutrophils can be depicted as both an antiinfectious and a proinflammatory cell. In cystic fibrosis there is an emerging picture of an imbalance between these two roles with both a reduction in the antiinfectious efficacy and an augmentation of the proinflammatory functions. Better knowledge of fundamental defects in neutrophil function in cystic fibrosis as well as a novel cellular function of CFTR, which will be reviewed, will allow identification of potentially new clinical targets and aid selective therapeutic action aimed at counteracting the lethal neutrophil-induced airway inflammation. The rationale for colchicine therapy is a significant example of a drug which might act both at the molecular levels on CFTR expression in epithelial cells and on neutrophils to mediate antiinflammatory effects. Preliminary results are presented in this issue (Med Inflamm 1999; 8: 13-15).
本假说的目的是为囊性纤维化中气道炎症的发病机制仍不明确这一问题提供新的见解。尽管囊性纤维化的遗传基础以及囊性纤维化跨膜传导调节因子（CFTR）的分子结构（导致该疾病的突变蛋白）已得到明确界定，但遗传缺陷与肺部病理生理学之间的明确关系，尤其是慢性感染和以中性粒细胞为主的气道炎症，尚未确立。因此，囊性纤维化是一种独特的病理情况，因为中性粒细胞既可以被描述为抗感染细胞，也可以被描述为促炎细胞。在囊性纤维化中，这两种作用之间出现了失衡的情况，抗感染功效降低，促炎功能增强。更好地了解囊性纤维化中性粒细胞功能的基本缺陷以及CFTR的一种新的细胞功能（将在本文中进行综述），将有助于识别潜在的新临床靶点，并有助于采取有针对性的治疗措施，以对抗致命的中性粒细胞诱导的气道炎症。秋水仙碱治疗的原理是一个重要的例子，说明一种药物可能在分子水平上作用于上皮细胞中CFTR的表达以及中性粒细胞，从而介导抗炎作用。本期发表了初步结果（《医学炎症》1999年；8：13 - 15）。
