Niles R M, Christensen T G, Breuer R, Stone P J, Snider G L
J Lab Clin Med. 1986 Nov;108(5):489-97.
The effects of several neurohumoral agents and serine proteases on glycoconjugate release from hamster tracheal organ cultures were assessed. The beta-adrenergic agonist isoproterenol inhibited glycoconjugate release, and its effect was abolished by the specific beta-blocking agent propranolol. A cholinergic agonist, pilocarpine, marginally increased glycoconjugate release, and its effect was abolished by the antagonist atropine. Human neutrophil elastase and porcine pancreatic trypsin consistently increased glycoconjugate release by 1.8 to 2.8-fold. When the proteases were inactivated, they were no longer effective in stimulating glycoconjugate release. Histologic and electron microscopic analysis of the protease-treated organ cultures revealed no discernible toxic reaction. In addition, organ cultures prelabeled with chromium 51 did not release an increased amount of radioactivity when treated with the proteases. Biochemical analysis of the glycoconjugates released into the culture medium showed them to be of high molecular weight (90% eluted in the void volume of a Sepharose 6B column) and to be resistant to digestion with hyaluronidase and heparinase, properties consistent with mucous glycoproteins. The mechanism of protease-induced glycoconjugate release is unknown. We speculate that stimulation of airway secretory cells by serine proteases of neutrophilic or other inflammatory cell origin may play a role in the increased airway secretion that is characteristic of acute tracheobronchitis.
评估了几种神经体液因子和丝氨酸蛋白酶对仓鼠气管器官培养物中糖缀合物释放的影响。β-肾上腺素能激动剂异丙肾上腺素抑制糖缀合物释放，其作用被特异性β-阻滞剂普萘洛尔消除。胆碱能激动剂毛果芸香碱略微增加糖缀合物释放，其作用被拮抗剂阿托品消除。人中性粒细胞弹性蛋白酶和猪胰蛋白酶一致地使糖缀合物释放增加1.8至2.8倍。当蛋白酶失活时，它们不再有效地刺激糖缀合物释放。对经蛋白酶处理的器官培养物进行组织学和电子显微镜分析，未发现明显的毒性反应。此外，用51铬预标记的器官培养物在用蛋白酶处理时不会释放出增加量的放射性。对释放到培养基中的糖缀合物进行生化分析，结果显示它们具有高分子量（90%在Sepharose 6B柱的空体积中洗脱）且对透明质酸酶和肝素酶消化具有抗性，这些特性与粘蛋白糖蛋白一致。蛋白酶诱导糖缀合物释放的机制尚不清楚。我们推测，中性粒细胞或其他炎症细胞来源的丝氨酸蛋白酶对气道分泌细胞的刺激可能在急性气管支气管炎特有的气道分泌增加中起作用。
