Jorens P G, Richman-Eisenstat J B, Housset B P, Massion P P, Ueki I, Nadel J A
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Eur Respir J. 1994 Nov;7(11):1925-31.
A bacteria-free supernatant of Pseudomonas aeruginosa induces the production of neutrophil chemotactic activity in human bronchial epithelial cells in vitro that is due to the potent chemotactic factor, interleukin-8 (IL-8). Because P. aeruginosa supernatant itself is not chemotactic, we hypothesized that intratracheal P. aeruginosa induces the production of neutrophil chemotactic factors, including IL-8, in vivo. Because neutrophils play a key role in cystic fibrosis, inhibition of neutrophil recruitment might be therapeutic. We studied the effect of P. aeruginosa supernatant in the isolated tracheal segment of dogs in vivo, and we measured neutrophil chemotactic activity in vitro in the tracheal fluid. We also determined the local effect of intratracheal administration of leumedin NPC 15669, an inhibitor of neutrophil recruitment, on IL-8- and Pseudomonas-induced neutrophil accumulation. P. aeruginosa supernatant and IL-8 both caused time-dependent accumulation of neutrophils in the tracheal fluid. Tracheal fluid obtained after P. aeruginosa administration had neutrophil chemotactic activity in vitro that was significantly inhibited by the IL-8 antibody. Intratracheal NPC 15669 prevented both IL-8- and Pseudomonas-induced accumulation of neutrophils. We conclude that P. aeruginosa supernatant recruits neutrophils into the airway indirectly by inducing the production of chemotactic factors, including IL-8. Our results suggest a potential therapeutic role for leumedins in chronic airway diseases.
铜绿假单胞菌的无菌上清液在体外可诱导人支气管上皮细胞产生中性粒细胞趋化活性，这是由于强效趋化因子白细胞介素-8（IL-8）所致。由于铜绿假单胞菌上清液本身并无趋化作用，我们推测气管内注入铜绿假单胞菌可在体内诱导包括IL-8在内的中性粒细胞趋化因子的产生。鉴于中性粒细胞在囊性纤维化中起关键作用，抑制中性粒细胞募集可能具有治疗作用。我们研究了铜绿假单胞菌上清液在犬离体气管段中的体内效应，并测定了气管液中的体外中性粒细胞趋化活性。我们还确定了气管内给予中性粒细胞募集抑制剂柳氮磺吡啶NPC 15669对IL-8和铜绿假单胞菌诱导的中性粒细胞积聚的局部影响。铜绿假单胞菌上清液和IL-8均导致气管液中中性粒细胞随时间依赖性积聚。给予铜绿假单胞菌后获得的气管液在体外具有中性粒细胞趋化活性，该活性被IL-8抗体显著抑制。气管内注入NPC 15669可预防IL-8和铜绿假单胞菌诱导的中性粒细胞积聚。我们得出结论，铜绿假单胞菌上清液通过诱导包括IL-8在内的趋化因子的产生，间接将中性粒细胞募集到气道中。我们的结果提示柳氮磺吡啶在慢性气道疾病中具有潜在的治疗作用。
