Richman-Eisenstat J B, Jorens P G, Hébert C A, Ueki I, Nadel J A
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Am J Physiol. 1993 Apr;264(4 Pt 1):L413-8. doi: 10.1152/ajplung.1993.264.4.L413.
Sputum from patients with cystic fibrosis, bronchiectasis, and chronic bronchitis contains neutrophils and neutrophil proteases, which have been implicated in the pathophysiology of mucus hypersecretion in airways. We asked whether interleukin-8 (IL-8), a potent neutrophil chemoattractant, might be involved in recruiting neutrophils into airways of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis. We found significant neutrophil chemotactic activity in sputum obtained from these patients. The IL-8 concentrations that we measured in sputum of patients with cystic fibrosis (7.1 +/- 1.0 x 10(-9) M, mean +/- SE), bronchiectasis (9.6 +/- 2.9 x 10(-9) M), and chronic bronchitis (2.8 +/- 1.0 x 10(-9) M) have been reported to cause significant chemotaxis in vitro and in airways in vivo, whereas concentrations measured in induced sputum from healthy subjects (1.1 +/- 0.3 x 10(-10) M) do not. A monoclonal antibody to IL-8 significantly inhibited the chemotactic activity in patients' sputum by 75-98%, but not in induced sputum from healthy subjects (9%). We conclude that IL-8 is an important chemotactic factor in sputum of patients with cystic fibrosis, bronchiectasis, and chronic bronchitis, and we suggest that IL-8 accounts, at least in part, for neutrophil recruitment into airways of patients with these diseases.
囊性纤维化、支气管扩张和慢性支气管炎患者的痰液中含有中性粒细胞和中性粒细胞蛋白酶,这些物质与气道黏液分泌过多的病理生理学有关。我们研究了白细胞介素-8(IL-8),一种有效的中性粒细胞趋化因子,是否参与将中性粒细胞募集到囊性纤维化、支气管扩张和慢性支气管炎患者的气道中。我们发现从这些患者获得的痰液中有显著的中性粒细胞趋化活性。我们在囊性纤维化患者痰液中测得的IL-8浓度(7.1±1.0×10⁻⁹M,平均值±标准误)、支气管扩张患者(9.6±2.9×10⁻⁹M)和慢性支气管炎患者(2.8±1.0×10⁻⁹M),据报道在体外和体内气道中均可引起显著的趋化作用,而健康受试者诱导痰液中测得的浓度(1.1±0.3×10⁻¹⁰M)则不会。一种抗IL-8单克隆抗体可使患者痰液中的趋化活性显著抑制75% - 98%,但对健康受试者诱导痰液中的趋化活性抑制作用不明显(9%)。我们得出结论,IL-8是囊性纤维化、支气管扩张和慢性支气管炎患者痰液中的一种重要趋化因子,我们认为IL-8至少部分地解释了中性粒细胞向这些疾病患者气道的募集。