Jorens P G, Richman-Eisenstat J B, Housset B P, Graf P D, Ueki I F, Olesch J, Nadel J A
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Am J Physiol. 1992 Dec;263(6 Pt 1):L708-13. doi: 10.1152/ajplung.1992.263.6.L708.
The neutrophil enzyme elastase is a potent secretagogue of airway secretory cells, and elastase is present in high concentrations in sputum of patients with hypersecretion (e.g., cystic fibrosis, bronchiectasis). Interleukin-8 (IL-8), a recently discovered cytokine with potent neutrophil chemotactic properties in vitro, is also found in the sputum of these patients. We used an isolated tracheal segment in dogs in vivo to study the effect of IL-8 in causing neutrophil accumulation, elastase release, and secretion (by measuring lysozyme concentrations) in the luminal superfusate. IL-8 caused a potent time-dependent neutrophil accumulation at between 3 and 6 h. The effect was significant at 10(-9) and maximum at 10(-8) M. No increase in free elastase, cathepsin G, or lysozyme was detected in the superfusate. Thus, in contrast to previous studies showing that ragweed antigen causes the accumulation of neutrophil elastase which in turn causes lysozyme secretion, IL-8 causes neutrophil accumulation without granule secretion (or subsequent secretagogue activity). The findings were confirmed with dog and human neutrophils in vitro.
中性粒细胞酶弹性蛋白酶是气道分泌细胞的一种强效促分泌剂，且在分泌亢进患者（如囊性纤维化、支气管扩张症患者）的痰液中浓度很高。白细胞介素-8（IL-8）是最近发现的一种在体外具有强效中性粒细胞趋化特性的细胞因子，在这些患者的痰液中也能发现。我们在体内使用犬的离体气管段来研究IL-8在引起中性粒细胞聚集、弹性蛋白酶释放以及管腔灌流液中分泌（通过测量溶菌酶浓度）方面的作用。IL-8在3至6小时内引起了强效的时间依赖性中性粒细胞聚集。该效应在10^(-9)时显著，在10^(-8)M时达到最大值。在灌流液中未检测到游离弹性蛋白酶、组织蛋白酶G或溶菌酶增加。因此，与先前显示豚草抗原导致中性粒细胞弹性蛋白酶聚集进而引起溶菌酶分泌的研究不同，IL-8引起中性粒细胞聚集但无颗粒分泌（或随后的促分泌活性）。这些发现通过体外犬和人类中性粒细胞得到了证实。
