Fick R B, Sonoda F, Hornick D B
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Semin Respir Infect. 1992 Sep;7(3):168-78.
Colonization in the respiratory tracts of cystic fibrosis (CF) patients by mucoid Pseudomonas aeruginosa correlates with the progression of bronchial airway pathology. There is a direct correlation between the incidence of Pseudomonas colonization and age, clinical score, extent of pulmonary disease, severity of radiographic changes, and level of serum immunoglobulins. The central propensity to Pseudomonas colonization in patients with CF is not freely understood, but we discuss the acquisition and persistence of P aeruginosa in the CF airway. Elucidation of pathogenetic mechanisms of CF inflammatory airways disease is the first essential step to initiating novel therapies. It has been difficult to prove that the ability of P aeruginosa to adhere to the respiratory epithelium and provide selective advantage for this gram-negative bacillus over other potential pathogens for infection in the CF airway. However, flexible filaments (pili) extending from the Pseudomonas cell wall are thought to medicate epithelial cell adherence for nonmucoid P aeruginosa, and similarly, the gelatinous exopolysaccharide alginate produced by mucoid variants of P aeruginosa seems to be the adhesive to tracheal cells. Following the signal event of adherence, this bacterial pathogen competes successfully for iron cofactor and multiplies, releasing proteases with broad substrate specificities that dramatically alter the airway antiprotease screen, and the pathogen creates defects in local antibacterial defenses. Lung inflammation in CF is characterized by massive neutrophil infiltration. Although critical to host defense, neutrophils also cause progressive airway damage by release of bioactive lipids, oxygen metabolites, and granule enzymes such as hydrolases, myeloperoxidase (MPO), lysozyme, and neutral serine proteases. The necessarily circumscribed discussion that follows will focus narrowly on the host cell-derived factors (macrophages and neutrophils) proposed as important components in this pathogenetic scheme.
黏液型铜绿假单胞菌在囊性纤维化（CF）患者呼吸道中的定植与支气管气道病理进展相关。铜绿假单胞菌定植的发生率与年龄、临床评分、肺部疾病程度、影像学改变的严重程度以及血清免疫球蛋白水平之间存在直接关联。CF患者对铜绿假单胞菌定植的内在倾向尚未完全明确，但我们将讨论铜绿假单胞菌在CF气道中的获得和持续存在情况。阐明CF炎性气道疾病的发病机制是启动新疗法的首要关键步骤。很难证明铜绿假单胞菌黏附于呼吸道上皮的能力，以及该革兰氏阴性杆菌相对于CF气道中其他潜在感染病原体具有选择性优势。然而，从铜绿假单胞菌细胞壁伸出的柔性细丝（菌毛）被认为介导非黏液型铜绿假单胞菌与上皮细胞的黏附，同样，黏液型铜绿假单胞菌变体产生的凝胶状胞外多糖藻酸盐似乎是与气管细胞的黏附剂。在黏附这一信号事件之后，这种细菌病原体成功竞争铁辅因子并繁殖，释放具有广泛底物特异性的蛋白酶，从而显著改变气道抗蛋白酶平衡，并且该病原体在局部抗菌防御中造成缺陷。CF中的肺部炎症以大量中性粒细胞浸润为特征。尽管中性粒细胞对宿主防御至关重要，但它们也通过释放生物活性脂质、氧代谢产物以及颗粒酶（如水解酶、髓过氧化物酶（MPO）、溶菌酶和中性丝氨酸蛋白酶）导致气道进行性损伤。接下来必然有限的讨论将狭义地聚焦于被认为是该发病机制中重要组成部分的宿主细胞衍生因子（巨噬细胞和中性粒细胞）。
